@article{Ormancey2023b,

title = {Complementary peptides represent a credible alternative to agrochemicals by activating translation of targeted proteins},

author = {M Ormancey and B Guillotin and R Merret and L Camborde and C Duboe and B Fabre and C Pouzet and F Impens and D Van Haver and M C Carpentier and H S Clemente and M Aguilar and D Lauressergues and L B Scharff and C Pichereaux and O Burlet-Schiltz and C Bousquet-Antonelli and K Gevaert and P Thuleau and S Plaza and J P Combier},

doi = {10.1038/s41467-023-35951-0},

issn = {2041-1723 (Electronic) 2041-1723 (Linking)},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Nat Commun},

volume = {14},

issue = {1},

pages = {254},

abstract = {The current agriculture main challenge is to maintain food production while facing multiple threats such as increasing world population, temperature increase, lack of agrochemicals due to health issues and uprising of weeds resistant to herbicides. Developing novel, alternative, and safe methods is hence of paramount importance. Here, we show that complementary peptides (cPEPs) from any gene can be designed to target specifically plant coding genes. External application of synthetic peptides increases the abundance of the targeted protein, leading to related phenotypes. Moreover, we provide evidence that cPEPs can be powerful tools in agronomy to improve plant traits, such as growth, resistance to pathogen or heat stress, without the needs of genetic approaches. Finally, by combining their activity they can also be used to reduce weed growth.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Arezki2022b,

title = {Surface charge influences protein corona, cell uptake and biological effects of carbon dots},

author = {Y Arezki and F Delalande and C Schaeffer-Reiss and S Cianferani and M Rapp and L Lebeau and F Pons and C Ronzani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36168840},

doi = {10.1039/d2nr03611h},

issn = {2040-3372 (Electronic) 2040-3364 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nanoscale},

abstract = {Carbon dots are emerging nanoparticles (NPs) with tremendous applications, especially in the biomedical field. Herein is reported the first quantitative proteomic analysis of the protein corona formed on CDs with different surface charge properties. Four CDs were synthesized from citric acid and various amine group-containing passivation reagents, resulting in cationic NPs with increasing zeta (zeta)-potential and density of positive charges. After CD contact with serum, we show that protein corona identity is influenced by CD surface charge properties, which in turn impacts CD uptake and viability loss in macrophages. In particular, CDs with high zeta-potential (+30 mV) and charge density (2 mumol mg(-1)) are the most highly internalized, and their cell uptake is strongly correlated with a corona enriched in vitronectin, fibulin, fetuin, adiponectin and alpha-glycoprotein. On the contrary, CDs with a lower zeta-potential (+11 mV) and charge density (0.01 mumol mg(-1)) are poorly internalized, while having a corona with a very different protein signature characterized by a high abundance of apolipoproteins (APOA1, APOB and APOC), albumin and hemoglobin. These data illustrate how corona characterization may contribute to a better understanding of CD cellular fate and biological effects, and provide useful information for the development of CDs for biomedical applications.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Filhol2022b,

title = {CK2β Is a Gatekeeper of Focal Adhesions Regulating Cell Spreading},

author = {Odile Filhol and Anne-Marie Hesse and Anne-Pascale Bouin and Corinne Albigès-Rizo and Florian Jeanneret and Christophe Battail and Delphine Pflieger and Claude Cochet},

doi = {10.3389/fmolb.2022.900947},

issn = {2296-889X},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Frontiers in Molecular Biosciences},

volume = {9},

pages = {900947},

abstract = {CK2 is a hetero-tetrameric serine/threonine protein kinase made up of two CK2α/α' catalytic subunits and two CK2β regulatory subunits. The free CK2α subunit and the tetrameric holoenzyme have distinct substrate specificity profiles, suggesting that the spatiotemporal organization of the individual CK2 subunits observed in living cells is crucial in the control of the many cellular processes that are governed by this pleiotropic kinase. Indeed, previous studies reported that the unbalanced expression of CK2 subunits is sufficient to drive epithelial to mesenchymal transition (EMT), a process involved in cancer invasion and metastasis. Moreover, sub-stoichiometric expression of CK2β compared to CK2α in a subset of breast cancer tumors was correlated with the induction of EMT markers and increased epithelial cell plasticity in breast carcinoma progression. Phenotypic changes of epithelial cells are often associated with the activation of phosphotyrosine signaling. Herein, using phosphotyrosine enrichment coupled with affinity capture and proteomic analysis, we show that decreased expression of CK2β in MCF10A mammary epithelial cells triggers the phosphorylation of a number of proteins on tyrosine residues and promotes the striking activation of the FAK1-Src-PAX1 signaling pathway. Moreover, morphometric analyses also reveal that CK2β loss increases the number and the spatial distribution of focal adhesion signaling complexes that coordinate the adhesive and migratory processes. Together, our findings allow positioning CK2β as a gatekeeper for cell spreading by restraining focal adhesion formation and invasion of mammary epithelial cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Beaussart2022b,

title = {Probing the mechanism of the peroxiredoxin decamer interaction with its reductase sulfiredoxin from the single molecule to the solution scale},

author = {A Beaussart and F Canonico and H Mazon and J Hidalgo and S Cianferani and H Le Cordier and A Kriznik and S Rahuel-Clermont},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35234779},

doi = {10.1039/d2nh00037g},

issn = {2055-6764 (Electronic) 2055-6756 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nanoscale Horiz},

volume = {7},

issue = {5},

pages = {515-525},

abstract = {Peroxiredoxins from the Prx1 subfamily (Prx) are highly regulated multifunctional proteins involved in oxidative stress response, redox signaling and cell protection. Prx is a homodimer that associates into a decamer. The monomer C-terminus plays intricate roles in Prx catalytic functions, decamer stability and interaction with its redox partner, the small reductase sulfiredoxin (Srx), that regulates the switching between Prx cellular functions. As only static structures of covalent Prx-Srx complexes have been reported, whether Srx binding dissociates the decameric assembly and how Prx subunit flexibility impacts complex formation are unknown. Here, we assessed the non-covalent interaction mechanism and dynamics in the solution of Saccharomyces cerevisiae Srx with the ten subunits of Prx Tsa1 at the decamer level via a combination of multiscale biophysical approaches including native mass spectrometry. We show that the ten subunits of the decamer can be saturated by ten Srx molecules and that the Tsa1 decamer in complex with Srx does not dissociate in solution. Furthermore, the binding events of atomic force microscopy (AFM) tip-grafted Srx molecules to Tsa1 individual subunits were relevant to the interactions between free molecules in solution. Combined with protein engineering and rapid kinetics, the observation of peculiar AFM force-distance signatures revealed that Tsa1 C-terminus flexibility controls Tsa1/Srx two-step binding and dynamics and determines the force-induced dissociation of Srx from each subunit of the decameric complex in a sequential or concerted mode. This combined approach from the solution to the single-molecule level offers promising prospects for understanding oligomeric protein interactions with their partners.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Awan2022b,

title = {Wnt5a Promotes Lysosomal Cholesterol Egress and Protects Against Atherosclerosis},

author = {S Awan and M Lambert and A Imtiaz and F Alpy and C Tomasetto and M Oulad-Abdelghani and C Schaeffer and C Moritz and D Julien-David and S Najib and L O Martinez and R L Matz and X Collet and R Silva-Rojas and J Bohm and J Herz and J Terrand and P Boucher},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34886684},

doi = {10.1161/CIRCRESAHA.121.318881},

issn = {1524-4571 (Electronic) 0009-7330 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Circ Res},

volume = {130},

issue = {2},

pages = {184-199},

abstract = {BACKGROUND: Impairment of cellular cholesterol trafficking is at the heart of atherosclerotic lesions formation. This involves egress of cholesterol from the lysosomes and 2 lysosomal proteins, the NPC1 (Niemann-Pick C1) and NPC2 that promotes cholesterol trafficking. However, movement of cholesterol out the lysosome and how disrupted cholesterol trafficking leads to atherosclerosis is unclear. As the Wnt ligand, Wnt5a inhibits the intracellular accumulation of cholesterol in multiple cell types, we tested whether Wnt5a interacts with the lysosomal cholesterol export machinery and studied its role in atherosclerotic lesions formation. METHODS: We generated mice deleted for the Wnt5a gene in vascular smooth muscle cells. To establish whether Wnt5a also protects against cholesterol accumulation in human vascular smooth muscle cells, we used a CRISPR/Cas9 guided nuclease approach to generate human vascular smooth muscle cells knockout for Wnt5a. RESULTS: We show that Wnt5a is a crucial component of the lysosomal cholesterol export machinery. By increasing lysosomal acid lipase expression, decreasing metabolic signaling by the mTORC1 (mechanistic target of rapamycin complex 1) kinase, and through binding to NPC1 and NPC2, Wnt5a senses changes in dietary cholesterol supply and promotes lysosomal cholesterol egress to the endoplasmic reticulum. Consequently, loss of Wnt5a decoupled mTORC1 from variations in lysosomal sterol levels, disrupted lysosomal function, decreased cholesterol content in the endoplasmic reticulum, and promoted atherosclerosis. CONCLUSIONS: These results reveal an unexpected function of the Wnt5a pathway as essential for maintaining cholesterol homeostasis in vivo.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Beinsteiner2022b,

title = {A novel nuclear receptor subfamily enlightens the origin of heterodimerization},

author = {B Beinsteiner and G V Markov and M Bourguet and A G McEwen and S Erb and A K M Patel and F Z El Khaloufi El Khaddar and C Lecroisey and G Holzer and K Essabri and I Hazemann and A Hamiche and S Cianferani and D Moras and V Laudet and I M L Billas},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36199108},

doi = {10.1186/s12915-022-01413-0},

issn = {1741-7007 (Electronic) 1741-7007 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {BMC Biol},

volume = {20},

issue = {1},

pages = {217},

abstract = {BACKGROUND: Nuclear receptors are transcription factors of central importance in human biology and associated diseases. Much of the knowledge related to their major functions, such as ligand and DNA binding or dimerization, derives from functional studies undertaken in classical model animals. It has become evident, however, that a deeper understanding of these molecular functions requires uncovering how these characteristics originated and diversified during evolution, by looking at more species. In particular, the comprehension of how dimerization evolved from ancestral homodimers to a more sophisticated state of heterodimers has been missing, due to a too narrow phylogenetic sampling. Here, we experimentally and phylogenetically define the evolutionary trajectory of nuclear receptor dimerization by analyzing a novel NR7 subgroup, present in various metazoan groups, including cnidarians, annelids, mollusks, sea urchins, and amphioxus, but lost in vertebrates, arthropods, and nematodes. RESULTS: We focused on NR7 of the cephalochordate amphioxus B. lanceolatum. We present a complementary set of functional, structural, and evolutionary analyses that establish that NR7 lies at a pivotal point in the evolutionary trajectory from homodimerizing to heterodimerizing nuclear receptors. The crystal structure of the NR7 ligand-binding domain suggests that the isolated domain is not capable of dimerizing with the ubiquitous dimerization partner RXR. In contrast, the full-length NR7 dimerizes with RXR in a DNA-dependent manner and acts as a constitutively active receptor. The phylogenetic and sequence analyses position NR7 at a pivotal point, just between the basal class I nuclear receptors that form monomers or homodimers on DNA and the derived class II nuclear receptors that exhibit the classical DNA-independent RXR heterodimers. CONCLUSIONS: Our data suggest that NR7 represents the "missing link" in the transition between class I and class II nuclear receptors and that the DNA independency of heterodimer formation is a feature that was acquired during evolution. Our studies define a novel paradigm of nuclear receptor dimerization that evolved from DNA-dependent to DNA-independent requirements. This new concept emphasizes the importance of DNA in the dimerization of nuclear receptors, such as the glucocorticoid receptor and other members of this pharmacologically important oxosteroid receptor subfamily. Our studies further underline the importance of studying emerging model organisms for supporting cutting-edge research.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis},

author = {M Bobowski-Gerard and C Boulet and F P Zummo and J Dubois-Chevalier and C Gheeraert and M Bou Saleh and J M Strub and A Farce and M Ploton and L Guille and J Vandel and A Bongiovanni and N Very and E Woitrain and A Deprince and F Lalloyer and E Bauge and L Ferri and L C Ntandja-Wandji and A K Cotte and C Grangette and E Vallez and S Cianferani and V Raverdy and R Caiazzo and V Gnemmi and E Leteurtre and B Pourcet and R Paumelle and K Ravnskjaer and G Lassailly and J T Haas and P Mathurin and F Pattou and L Dubuquoy and B Staels and P Lefebvre and J Eeckhoute},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36088459},

doi = {10.1038/s41467-022-33063-9},

issn = {2041-1723 (Electronic) 2041-1723 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nat Commun},

volume = {13},

issue = {1},

pages = {5324},

abstract = {Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analyses unraveling Basonuclin 2 (BNC2) as a myofibroblast identity transcription factor. Using liver fibrosis as a model for in-depth investigations, we first show that BNC2 expression is induced in both mouse and human fibrotic livers from different etiologies and decreases upon human liver fibrosis regression. Importantly, we found that BNC2 transcriptional induction is a specific feature of myofibroblastic activation in fibrotic tissues. Mechanistically, BNC2 expression and activities allow to integrate pro-fibrotic stimuli, including TGFbeta and Hippo/YAP1 signaling, towards induction of matrisome genes such as those encoding type I collagen. As a consequence, Bnc2 deficiency blunts collagen deposition in livers of mice fed a fibrogenic diet. Additionally, our work establishes BNC2 as potentially druggable since we identified the thalidomide derivative CC-885 as a BNC2 inhibitor. Altogether, we propose that BNC2 is a transcription factor involved in canonical pathways driving myofibroblastic activation in fibrosis.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Boutin2022b,

title = {Measuring the NQO2: Melatonin Complex by Native Nano-Electrospray Ionization Mass Spectrometry},

author = {J A Boutin and J Stojko and G Ferry and S Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36180703},

doi = {10.1007/978-1-0716-2593-4_34},

issn = {1940-6029 (Electronic) 1064-3745 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Methods Mol Biol},

volume = {2550},

pages = {323-328},

abstract = {Melatonin exerts its effects through a series of target proteins/receptors and enzymes. Its antioxidant capacity might be due to its capacity to inhibit a quinone reductase (NQO2) at high concentration (50 muM). Demonstrating the existence of a complex between a compound and a protein is often not easy. It requires either that the compound is an inhibitor-and the complex translates by an inhibition of the catalytic activity-or the compound is radiolabeled-and the complex translates in standard binding approaches, such as in receptology. Outside these two cases, the detection of the protein:small molecule complexes by mass spectrometry has recently been made possible, thanks to the development of so-called native mass spectrometry. Using this approach, one can measure masses corresponding to an intact noncovalent complex between a compound and its target, usually after titration or competition experiments. In the present chapter, we detail the characterization of NQO2:melatonin interaction using native mass spectrometry.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brun2022b,

title = {Resistance to glycation in the zebra finch: Mass spectrometry-based analysis and its perspectives for evolutionary studies of aging},

author = {C Brun and O Hernandez-Alba and A Hovasse and F Criscuolo and C Schaeffer-Reiss and F Bertile},

url = {<Go to ISI>://WOS:000799037700003},

doi = {ARTN 111811 10.1016/j.exger.2022.111811},

issn = {0531-5565},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Experimental Gerontology},

volume = {164},

abstract = {In humans, hyperglycemia is associated with protein glycation, which may contribute to aging. Strikingly, birds usually outlive mammals of the same body mass, while exhibiting high plasma glucose levels. However, how birds succeed in escaping pro-aging effects of glycation remains unknown. Using a specific mass spectrometrybased approach in captive zebra finches of known age, we recorded high glycaemia values but no glycated hemoglobin form was found. Still, we showed that zebra finch hemoglobin can be glycated in vitro, albeit only to a limited extent compared to its human homologue. This may be due to peculiar structural features, as supported by the unusual presence of three different tetramer populations with balanced proportions and a still bound cofactor that could be inositol pentaphosphate. High levels of the glycated forms of zebra finch plasma serotransferrin, carbonic anhydrase 2, and albumin were measured. Glucose, age or body mass correlations with either plasma glycated proteins or hemoglobin isoforms suggest that those variables may be future molecular tools of choice to monitor glycation and its link with individual fitness. Our molecular advance may help determine how evolution succeeded in associating flying ability, high blood glucose and long lifespan in birds.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cavazza2022b,

title = {Proteomic analysis of Rhodospirillum rubrum after carbon monoxide exposure reveals an important effect on metallic cofactor biosynthesis},

author = {C Cavazza and V Collin-Faure and J Perard and H Diemer and S Cianferani and T Rabilloud and E Darrouzet},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34601154},

doi = {10.1016/j.jprot.2021.104389},

issn = {1876-7737 (Electronic) 1874-3919 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {J Proteomics},

volume = {250},

pages = {104389},

abstract = {Some carboxydotrophs like Rhodospirillum rubrum are able to grow with CO as their sole source of energy using a Carbone monoxide dehydrogenase (CODH) and an Energy conserving hydrogenase (ECH) to perform anaerobically the so called water-gas shift reaction (WGSR) (CO + H2O – CO2 + H2). Several studies have focused at the biochemical and biophysical level on this enzymatic system and a few OMICS studies on CO metabolism. Knowing that CO is toxic in particular due to its binding to heme iron atoms, and is even considered as a potential antibacterial agent, we decided to use a proteomic approach in order to analyze R. rubrum adaptation in term of metabolism and management of the toxic effect. In particular, this study allowed highlighting a set of proteins likely implicated in ECH maturation, and important perturbations in term of cofactor biosynthesis, especially metallic cofactors. This shows that even this CO tolerant microorganism cannot avoid completely CO toxic effects associated with its interaction with metallic ions. SIGNIFICANCE: This proteomic study highlights the fact that even in a microorganism able to handle carbon monoxide and in some way detoxifying it via the intrinsic action of the carbon monoxide dehydrogenase (CODH), CO has important effects on metal homeostasis, metal cofactors and metalloproteins. These effects are direct or indirect via transcription regulation, and amplified by the high interdependency of cofactors biosynthesis.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chazarin2022b,

title = {Molecular Liver Fingerprint Reflects the Seasonal Physiology of the Grey Mouse Lemur (Microcebus murinus) during Winter},

author = {B Chazarin and M Benhaim-Delarbre and C Brun and A Anzeraey and F Bertile and J Terrien},

url = {<Go to ISI>://WOS:000785517200001},

doi = {ARTN 4254 10.3390/ijms23084254},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

issue = {8},

abstract = {Grey mouse lemurs (Microcebus murinus) are primates that respond to environmental energetic constraints through strong physiological seasonality. They notably fatten during early winter (EW), and mobilize their lipid reserves while developing glucose intolerance during late winter (LW), when food availability is low. To decipher how the hepatic mechanisms may support such metabolic flexibility, we analyzed the liver proteome of adult captive male mouse lemurs, whose seasonal regulations are comparable to their wild counterparts. We highlight profound hepatic changes that reflect fat accretion in EW at the whole-body level, without triggering an ectopic storage of fat in the liver, however. Moreover, molecular regulations are consistent with the decrease in liver glucose utilization in LW, and therefore with reduced tolerance to glucose. However, no major regulation was seen in insulin signaling/resistance pathways. Fat mobilization in LW appeared possibly linked to the reactivation of the reproductive system while enhanced liver detoxification may reflect an anticipation to return to summer levels of food intake. Overall, these results show that the physiology of mouse lemurs during winter relies on solid molecular foundations in liver processes to adapt fuel partitioning while opposing the development of a pathological state despite large lipid fluxes.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chion2022b,

title = {Accounting for multiple imputation-induced variability for differential analysis in mass spectrometry-based label-free quantitative proteomics},

author = {M Chion and C Carapito and F Bertrand},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36037245},

doi = {10.1371/journal.pcbi.1010420},

issn = {1553-7358 (Electronic) 1553-734X (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {PLoS Comput Biol},

volume = {18},

issue = {8},

pages = {e1010420},

abstract = {Imputing missing values is common practice in label-free quantitative proteomics. Imputation aims at replacing a missing value with a user-defined one. However, the imputation itself may not be optimally considered downstream of the imputation process, as imputed datasets are often considered as if they had always been complete. Hence, the uncertainty due to the imputation is not adequately taken into account. We provide a rigorous multiple imputation strategy, leading to a less biased estimation of the parameters' variability thanks to Rubin's rules. The imputation-based peptide's intensities' variance estimator is then moderated using Bayesian hierarchical models. This estimator is finally included in moderated t-test statistics to provide differential analyses results. This workflow can be used both at peptide and protein-level in quantification datasets. Indeed, an aggregation step is included for protein-level results based on peptide-level quantification data. Our methodology, named mi4p, was compared to the state-of-the-art limma workflow implemented in the DAPAR R package, both on simulated and real datasets. We observed a trade-off between sensitivity and specificity, while the overall performance of mi4p outperforms DAPAR in terms of F-Score.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Does size matter? A proteomics-informed comparison of the effects of polystyrene beads of different sizes on macrophages},

author = {V Collin-Faure and B Dalzon and J Devcic and H Diemer and S Cianferani and T Rabilloud},

url = {<Go to ISI>://WOS:000820824900001},

doi = {10.1039/d2en00214k},

issn = {2051-8153},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Environmental Science-Nano},

volume = {9},

issue = {8},

pages = {2827-2840},

abstract = {Plastics are one of the most preoccupying emerging pollutants. Macroplastics released into the environment degrade into microplastics and nanoplastics. Because of their small size, these micro and nano plastic particles can enter the food chain and, in addition to their ecotoxicological effects, contaminate humans with still unknown biological effects. Plastics being particulate pollutants, they are handled in the human body by scavenger cells such as macrophages, which are important players in the immune system. In order to get a better appraisal of the effects of plastic particles on macrophages, we have studied the effects of unmodified polystyrene particles of 0.1, 1 and 10 micrometers of diameter, by a combination of proteomics and targeted validation experiments. Proteomics showed important adaptive changes of the proteome in response to exposure to plastics, with more than one third of the detected proteins showing a significance change in their abundance in response to cell exposure to at least one plastic bead size. These changes affected for example mitochondrial, lysosomal or cytoskeletal proteins. Although an increase in the mitochondrial transmembrane potential was detected in response to 10 micrometer beads, no alteration in cell viability was observed. Similarly, no lysosomal dysfunction and no alteration in the phagocytic capability of the cells was observed in response to exposure to plastics. When the inflammatory response was examined, no increase in the secretion of tumor necrosis factor or interleukin 6 was observed. Oppositely, the secretion of these cytokines in response to lipopolysaccharide was observed after exposure to plastics, which suggested a decreased ability of macrophages to respond to bacterial infection. In conclusion, these results provide a better understanding of the responses of macrophages to exposure to polystyrene particles of different sizes.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cotin2022b,

title = {A Confinement-Driven Nucleation Mechanism of Metal Oxide Nanoparticles Obtained via Thermal Decomposition in Organic Media},

author = {G Cotin and B Heinrich and F Perton and C Kiefer and G Francius and D Mertz and B Freis and B Pichon and J M Strub and S Cianferani and N Ortiz Pena and D Ihiawakrim and D Portehault and O Ersen and A Khammari and M Picher and F Banhart and C Sanchez and S Begin-Colin},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35426247},

doi = {10.1002/smll.202200414},

issn = {1613-6829 (Electronic) 1613-6810 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Small},

volume = {18},

issue = {20},

pages = {e2200414},

abstract = {Thermal decomposition is a very efficient synthesis strategy to obtain nanosized metal oxides with controlled structures and properties. For the iron oxide nanoparticle synthesis, it allows an easy tuning of the nanoparticle's size, shape, and composition, which is often explained by the LaMer theory involving a clear separation between nucleation and growth steps. Here, the events before the nucleation of iron oxide nanocrystals are investigated by combining different complementary in situ characterization techniques. These characterizations are carried out not only on powdered iron stearate precursors but also on a preheated liquid reaction mixture. They reveal a new nucleation mechanism for the thermal decomposition method: instead of a homogeneous nucleation, the nucleation occurs within vesicle-like-nanoreactors confining the reactants. The different steps are: 1) the melting and coalescence of iron stearate particles, leading to "droplet-shaped nanostructures" acting as nanoreactors; 2) the formation of a hitherto unobserved iron stearate crystalline phase within the nucleation temperature range, simultaneously with stearate chains loss and Fe(III) to Fe(II) reduction; 3) the formation of iron oxide nuclei inside the nanoreactors, which are then ejected from them. This mechanism paves the way toward a better mastering of the metal oxide nanoparticles synthesis and the control of their properties.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Colome2022d,

title = {Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis},

author = {N Colome and J Abian and K Aloria and J M Arizmendi and S Barcelo-Batllori and S Braga-Lagache and O Burlet-Schiltz and M Carrascal and J I Casal and E Chicano-Galvez and C Chiva and L F Clemente and F Elortza and J M Estanyol and J Fernandez-Irigoyen and P Fernandez-Puente and M J Fidalgo and C Froment and M Fuentes and C Fuentes-Almagro and M Gay and A Hainard and M Heller and M L Hernandez and N Ibarrola and I Iloro and T Kieselbach and A Lario and M Locard-Paulet and A Marina-Ramirez and L Martin and E Morato-Lopez and J Munoz and R Navajas and M A Odena and L Odriozola and E Oliveira and A Paradela and C Pasquarello and V Los Rios and C Ruiz-Romero and E Sabido and M Sanchez Del Pino and J Sancho and E Santamaria and C Schaeffer-Reiss and J Schneider and C Torre and M L Valero and M Vilaseca and S Wu and L Wu and P Embun and F Canals and F J Corrales and Isciii ProteoRed and EuPa},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34758407},

doi = {10.1016/j.jprot.2021.104409},

issn = {1876-7737 (Electronic) 1874-3919 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {J Proteomics},

volume = {251},

pages = {104409},

abstract = {Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows. Aiming to investigate the effect of different variables in the performance of proteome wide phosphoprotein analysis protocols, ProteoRed-ISCIII and EuPA launched the Proteomics Multicentric Experiment 11 (PME11). A reference sample consisting of a yeast protein extract spiked in with different amounts of a phosphomix standard (Sigma/Merck) was distributed to 31 laboratories around the globe. Thirty-six datasets from 23 laboratories were analyzed. Our results indicate the suitability of the PME11 reference sample to benchmark and optimize phosphoproteomics strategies, weighing the influence of different factors, as well as to rank intra and inter laboratory performance.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Darriere2022b,

title = {Upon heat stress processing of ribosomal RNA precursors into mature rRNAs is compromised after cleavage at primary P site in Arabidopsis thaliana},

author = {T Darriere and E Jobet and D Zavala and M L Escande and N Durut and A Bures and F Blanco-Herrera and E A Vidal and M Rompais and C Carapito and S Gourbiere and J Saez-Vasquez},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35522061},

doi = {10.1080/15476286.2022.2071517},

issn = {1555-8584 (Electronic) 1547-6286 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {RNA Biol},

volume = {19},

issue = {1},

pages = {719-734},

abstract = {Transcription and processing of 45S rRNAs in the nucleolus are keystones of ribosome biogenesis. While these processes are severely impacted by stress conditions in multiple species, primarily upon heat exposure, we lack information about the molecular mechanisms allowing sessile organisms without a temperature-control system, like plants, to cope with such circumstances. We show that heat stress disturbs nucleolar structure, inhibits pre-rRNA processing and provokes imbalanced ribosome profiles in Arabidopsis thaliana plants. Notably, the accuracy of transcription initiation and cleavage at the primary P site in the 5'ETS (5' External Transcribed Spacer) are not affected but the levels of primary 45S and 35S transcripts are, respectively, increased and reduced. In contrast, precursors of 18S, 5.8S and 25S RNAs are rapidly undetectable upon heat stress. Remarkably, nucleolar structure, pre-rRNAs from major ITS1 processing pathway and ribosome profiles are restored after returning to optimal conditions, shedding light on the extreme plasticity of nucleolar functions in plant cells. Further genetic and molecular analysis to identify molecular clues implicated in these nucleolar responses indicate that cleavage rate at P site and nucleolin protein expression can act as a checkpoint control towards a productive pre-rRNA processing pathway.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Declercq2022b,

title = {MS(2)Rescore: Data-driven rescoring dramatically boosts immunopeptide identification rates},

author = {A Declercq and R Bouwmeester and A Hirschler and C Carapito and S Degroeve and L Martens and R Gabriels},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35803561},

doi = {10.1016/j.mcpro.2022.100266},

issn = {1535-9484 (Electronic) 1535-9476 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Mol Cell Proteomics},

pages = {100266},

abstract = {Immunopeptidomics aims to identify Major Histocompatibility Complex-presented peptides on almost all cell that can be used in anti-cancer vaccine development. However, existing immunopeptidomics data analysis pipelines suffer from the non-tryptic nature of immunopeptides, complicating their identification. Previously, peak intensity predictions by MS(2)PIP and retention time predictions by DeepLC, have been shown to improve tryptic peptide identifications when rescoring peptide-spectrum matches with Percolator. However, as MS(2)PIP was tailored towards tryptic peptides, we have here retrained MS(2)PIP to include non-tryptic peptides. Interestingly, the new models not only greatly improve predictions for immunopeptides, but also yield further improvements for tryptic peptides. We show that the integration of new MS(2)PIP models, DeepLC, and Percolator in one software package, MS(2)Rescore, increases spectrum identification rate and unique identified peptides with 46% and 36% compared to standard Percolator rescoring at 1% FDR. Moreover, MS(2)Rescore also outperforms the current state-of-the-art in immunopeptide-specific identification approaches. Altogether, MS(2)Rescore thus allows substantially improved identification of novel epitopes from existing immunopeptidomics workflows.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Desligniere2022d,

title = {A Combination of Native LC-MS Approaches for the Comprehensive Characterization of the Antibody-Drug Conjugate Trastuzumab Deruxtecan},

author = {E Desligniere and H Diemer and S Erb and P Coliat and X Pivot and A Detappe and O Hernandez-Alba and S Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36336868},

doi = {10.31083/j.fbl2710290},

issn = {2768-6698 (Electronic) 2768-6698 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Front Biosci (Landmark Ed)},

volume = {27},

issue = {10},

pages = {290},

abstract = {BACKGROUND: Native mass spectrometry (nMS) approaches appear attractive to complement bottom-up strategies traditionally used in biopharmaceutical industries thanks to their quite straightforward and rapid workflows, especially through online hyphenation of non-denaturing liquid chromatography (LC) to nMS. The present work provides an overview of the state-of-the-art chromatographic tools available for the detailed characterization of monoclonal antibody (mAb) formats, exemplified on the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd). METHODS: T-DXd was first characterized by conventional reversed phase LC (rpLC) and peptide mapping. Couplings of size exclusion chromatography (SEC), cation exchange chromatography (CEX), and hydrophobic interaction chromatography (HIC) to nMS were used to gain further insights into size, hydrophobic, and charge variants of T-DXd and its parental mAb trastuzumab, at intact and middle-up levels. RESULTS: SEC-nMS first offered a direct snapshot of the homogeneous conjugation of T-DXd, with an average drug-to-antibody ratio (DAR) of 8 in agreement with a conjugation on cysteines after reduction of all interchain disulfide bonds. Moreover, SEC-nMS afforded precise identification and quantification of aggregates and fragments. Middle-up level experiments performed after IdeS digestion confirmed that drug conjugation occurs in the Fab region of the mAb, as seen with rpLC. HIC separated two DAR8 species that could not be differentiated by nMS. Although middle-up HIC-nMS proved to be more informative for oxidized forms, the identification of minor variants was still difficult because of poor MS signal quality, showing how the coupling of HIC to nMS remains challenging. Lastly, middle-up CEX-nMS provided accurate determination and localization of post-translational modifications, with several acidic/basic variants within Fab and Fc regions of T-DXd that were also identified by peptide mapping. CONCLUSIONS: This study illustrates the strengths and drawbacks of each LC-nMS coupling. By combining SEC-, HIC-, and CEX-nMS, we were able to achieve a comprehensive characterization of T-DXd without extensive sample preparation prior to MS analysis.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Advanced IM-MS-based Approaches for Protein Analysis: Collision-induced Unfolding (CIU) and Hyphenation of Liquid Chromatography to IM-MS},

author = {E Deslignière and O Hernandez-Alba and S Cianférani},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {in New developemnts in MS : ion -mobility Mass Spectrometry},

volume = {chapter 16},

pages = {436-460},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Desligniere2022c,

title = {Combination of IM-Based Approaches to Unravel the Coexistence of Two Conformers on a Therapeutic Multispecific mAb},

author = {E Desligniere and S Ollivier and A Ehkirch and A Martelet and D Ropartz and N Lechat and O Hernandez-Alba and J M Menet and S Clavier and H Rogniaux and B Genet and S Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35604400},

doi = {10.1021/acs.analchem.2c00928},

issn = {1520-6882 (Electronic) 0003-2700 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Anal Chem},

volume = {94},

issue = {22},

pages = {7981-7989},

abstract = {Multispecific antibodies, which target multiple antigens at once, are emerging as promising therapeutic entities to offer more effective treatment than conventional monoclonal antibodies (mAbs). However, these highly complex mAb formats pose significant analytical challenges. We report here on the characterization of a trispecific antibody (tsAb), which presents two isomeric forms clearly separated and identified with size exclusion chromatography coupled to native mass spectrometry (SEC-nMS). Previous studies showed that these isomers might originate from a proline cis/trans isomerization in one Fab subunit of the tsAb. We combined several innovative ion mobility (IM)-based approaches to confirm the isomeric nature of the two species and to gain new insights into the conformational landscape of both isomers. Preliminary SEC-nIM-MS measurements performed on a low IM resolution instrument provided the first hints of the coexistence of different conformers, while complementary collision-induced unfolding (CIU) experiments evidenced distinct gas-phase unfolding behaviors upon activation for the two isomers. As subtle conformational differences remained poorly resolved on our early generation IM platform, we performed high-resolution cyclic IM (cIM-MS) to unambiguously conclude on the coexistence of two conformers. The cis/trans equilibrium was further tackled by exploiting the IM(n) slicing capabilities of the cIM-MS instrument. Altogether, our results clearly illustrate the benefits of combining state-of-the-art nMS and IM-MS approaches to address challenging issues encountered in biopharma. As engineered antibody constructs become increasingly sophisticated, CIU and cIM-MS methodologies undoubtedly have the potential to integrate the drug development analytical toolbox to achieve in-depth conformational characterization of these products.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Deciphering cellular and molecular determinants of human DPCD protein in complex with RUVBL1/RUVBL2 AAA-ATPases},

author = {R Dos Santos Morais and P E Santo and M Ley and C Schelcher and Y Abel and L Plassart and E Desligniere and M E Chagot and M Quinternet and A C F Paiva and S Hessmann and N Morellet and M F Sousa P and F Vandermoere and E Bertrand and B Charpentier and T M Bandeiras and C Plisson-Chastang and C Verheggen and S Cianferani and X Manival},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35901867},

doi = {10.1016/j.jmb.2022.167760},

issn = {1089-8638 (Electronic) 0022-2836 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {J Mol Biol},

volume = {434},

issue = {19},

pages = {167760},

abstract = {DPCD is a protein that may play a role in cilia formation and whose absence leads to primary ciliary dyskinesia (PCD), a rare disease caused by impairment of ciliated cells. Except for high-throughput studies that identified DPCD as a possible RUVBL1 (R1) and RUVBL2 (R2) partner, no in-depth cellular, biochemical, and structural investigation involving DPCD have been reported so far. R1 and R2 proteins are ubiquitous highly conserved AAA + family ATPases that assemble and mature a plethora of macromolecular complexes and are pivotal in numerous cellular processes, especially by guaranteeing a co-chaperoning function within R2TP or R2TP-like machineries. In the present study, we identified DPCD as a new R1R2 partner in vivo. We show that DPCD interacts directly with R1 and R2 in vitro and in cells. We characterized the physico-chemical properties of DPCD in solution and built a 3D model of DPCD. In addition, we used a variety of orthogonal biophysical techniques including small-angle X-ray scattering, structural mass spectrometry and electron microscopy to assess the molecular determinants of DPCD interaction with R1R2. Interestingly, DPCD disrupts the dodecameric state of R1R2 complex upon binding and this interaction occurs mainly via the DII domains of R1R2.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fadel2022b,

title = {Insights into the atypical autokinase activity of the Pseudomonas aeruginosa GacS histidine kinase and its interaction with RetS},

author = {F Fadel and V Bassim and V I Francis and S L Porter and T Botzanowski and P Legrand and M M Perez and Y Bourne and S Cianferani and F Vincent},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35767996},

doi = {10.1016/j.str.2022.06.002},

issn = {1878-4186 (Electronic) 0969-2126 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Structure},

abstract = {Virulence in Pseudomonas aeruginosa (PA) depends on complex regulatory networks, involving phosphorelay systems based on two-component systems (TCSs). The GacS/GacA TCS is a master regulator of biofilm formation, swarming motility, and virulence. GacS is a membrane-associated unorthodox histidine kinase (HK) whose phosphorelay signaling pathway is inhibited by the RetS hybrid HK. Here we provide structural and functional insights into the interaction of GacS with RetS. The structure of the GacS-HAMP-H1 cytoplasmic regions reveals an unusually elongated homodimer marked by a 135 A long helical bundle formed by the HAMP, the signaling helix (S helix) and the DHp subdomain. The HAMP and S helix regions are essential for GacS signaling and contribute to the GacS/RetS binding interface. The structure of the GacS D1 domain together with the discovery of an unidentified functional ND domain, essential for GacS full autokinase activity, unveils signature motifs in GacS required for its atypical autokinase mechanism.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Knighton2022b,

title = {Upconversion in a d-f [RuYb3] Supramolecular Assembly},

author = {R C Knighton and L K Soro and W Thor and J M Strub and S Cianferani and Y Mely and M Lenertz and K L Wong and C Platas-Iglesias and F Przybilla and L J Charbonniere},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35771602},

doi = {10.1021/jacs.2c05037},

issn = {1520-5126 (Electronic) 0002-7863 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {J Am Chem Soc},

abstract = {We have prepared a hetero-tetrametallic assembly consisting of three ytterbium ions coordinated to a central [Ru(bpm)3](2+) (bpm = 2,2'-bipyrimidine) motif. Irradiation into the absorption band of the peripheral ytterbium ions at 980 nm engenders emission of the (3)MLCT state of the central [Ru(bpm)3](2+) core at 636 nm, which represents the first example of f – d molecular upconversion (UC). Time-resolved measurements reveal a slow rise of the UC emission, which was modeled with a mathematical treatment of the observed kinetics according to a cooperative photosensitization mechanism using a virtual Yb centered doubly excited state followed by energy transfer to the Ru centered (1)MLCT state.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Poignavent2022b,

title = {A flexible and original architecture of two unrelated zinc fingers underlies the role of the multitask P1 in RYMV spread},

author = {V Poignavent and F Hoh and G Terral and Y Yang and F X Gillet and J H Kim and F Allemand and E Lacombe and C Brugidou and S Cianferani and H Demene and F Vignols},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35798161},

doi = {10.1016/j.jmb.2022.167715},

issn = {1089-8638 (Electronic) 0022-2836 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {J Mol Biol},

pages = {167715},

abstract = {Viruses of the sobemovirus genus are plant viruses, most of which generate very important agricultural and financial losses. Among them, the rice yellow mottle virus (RYMV) is one of the most damaging pathogens devastating rice fields in Africa. RYMV infectivity and propagation rely on its protein P1, identified as a key movement and potential long-distance RNA silencing suppressor. Here we describe P1's complete 3D structure and dynamics obtained by an integrative approach combining X-Ray crystallography and NMR spectroscopy. We show that P1 is organized in two semi-independent and topologically unrelated domains, each harboring an original zinc finger. The two domains exhibit different affinities for zinc and sensitivities to oxidoreduction conditions, making the C-terminal P1 region a potential labile sensor of the plant redox status. An additional level of regulation resides on the capacity of P1 to oligomerize through its N-terminal domain. Coupling P1 structure information with site-directed mutagenesis and plant functional assays, we identified key residues in each zinc domain essential for infectivity and spread in rice tissues. Altogether, our results provide the first complete structure of a sobemoviral P1 movement protein and highlight structural and dynamical properties that may serve RYMV functions to infect and invade its host plant.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Quque2022b,

title = {Eusociality is linked to caste-specific differences in metabolism, immune system, and somatic maintenance-related processes in an ant species},

author = {M Quque and C Villette and F Criscuolo and C Sueur and F Bertile and D Heintz},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34971425},

doi = {10.1007/s00018-021-04024-0},

issn = {1420-9071 (Electronic) 1420-682X (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Cell Mol Life Sci},

volume = {79},

issue = {1},

pages = {29},

abstract = {The social organization of many primate, bird and rodent species and the role of individuals within that organization are associated with specific individual physiological traits. However, this association is perhaps most pronounced in eusocial insects (e.g., termites, ants). In such species, genetically close individuals show significant differences in behavior, physiology, and life expectancy. Studies addressing the metabolic changes according to the social role are still lacking. We aimed at understanding how sociality could influence essential molecular processes in a eusocial insect, the black garden ant (Lasius niger) where queens can live up to ten times longer than workers. Using mass spectrometry-based analysis, we explored the whole metabolome of queens, nest-workers and foraging workers. A former proteomics study done in the same species allowed us to compare the findings of both approaches. Confirming the former results at the proteome level, we showed that queens had fewer metabolites related to immunity. Contrary to our predictions, we did not find any metabolite linked to reproduction in queens. Among the workers, foragers had a metabolic signature reflecting a more stressful environment and a more highly stimulated immune system. We also found that nest-workers had more digestion-related metabolites. Hence, we showed that specific metabolic signatures match specific social roles. Besides, we identified metabolites differently expressed among behavioral castes and involved in nutrient sensing and longevity pathways (e.g., sirtuins, FOXO). The links between such molecular pathways and aging being found in an increasing number of taxa, our results confirm and strengthen their potential universality.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rady2022b,

title = {A Novel Family of Acid-Cleavable Linker Based on Cyclic Acetal Motifs for the Production of Antibody-Drug Conjugates with High Potency and Selectivity},

author = {T Rady and L Turelli and M Nothisen and E Tobaldi and S Erb and F Thoreau and O Hernandez-Alba and S Cianferani and F Daubeuf and A Wagner and G Chaubet},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36106863},

doi = {10.1021/acs.bioconjchem.2c00314},

issn = {1520-4812 (Electronic) 1043-1802 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Bioconjug Chem},

abstract = {Cleavable linkers have become the subject of intense study in the field of chemical biology, particularly because of their applications in the construction of antibody-drug conjugates (ADC), where they facilitate lysosomal cleavage and liberation of drugs from their carrier protein. Due to lysosomes' acidic nature, acid-labile motifs have attracted much attention, leading to the development of hydrazone and carbonate linkers among several other entities. Continuing our efforts in designing new moieties, we present here a family of cyclic acetals that exhibit excellent plasma stability and acid lability, notably in lysosomes. Incorporated in ADC, they led to potent constructs with picomolar potency in vitro and similar in vivo efficacy as the commercially available ADC Kadcyla in mouse xenograft models.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sicoli2022b,

title = {Large-Scale Conformational Changes of FhaC Provide Insights Into the Two-Partner Secretion Mechanism},

author = {G Sicoli and A Konijnenberg and J Guerin and S Hessmann and E Del Nero and O Hernandez-Alba and S Lecher and G Rouaut and L Mueggenburg and H Vezin and S Cianferani and F Sobott and R Schneider and F Jacob-Dubuisson},

url = {<Go to ISI>://WOS:000837116500001},

doi = {ARTN 950871 10.3389/fmolb.2022.950871},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Frontiers in Molecular Biosciences},

volume = {9},

abstract = {The Two-Partner secretion pathway mediates protein transport across the outer membrane of Gram-negative bacteria. TpsB transporters belong to the Omp85 superfamily, whose members catalyze protein insertion into, or translocation across membranes without external energy sources. They are composed of a transmembrane beta barrel preceded by two periplasmic POTRA domains that bind the incoming protein substrate. Here we used an integrative approach combining in vivo assays, mass spectrometry, nuclear magnetic resonance and electron paramagnetic resonance techniques suitable to detect minor states in heterogeneous populations, to explore transient conformers of the TpsB transporter FhaC. This revealed substantial, spontaneous conformational changes on a slow time scale, with parts of the POTRA2 domain approaching the lipid bilayer and the protein's surface loops. Specifically, our data indicate that an amphipathic POTRA2 beta hairpin can insert into the beta barrel. We propose that these motions enlarge the channel and initiate substrate secretion. Our data propose a solution to the conundrum how TpsB transporters mediate protein secretion without the need for cofactors, by utilizing intrinsic protein dynamics.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sebastiani2022b,

title = {Structural and Biochemical Investigation of the Heterodimeric Murine tRNA-Guanine Transglycosylase},

author = {M Sebastiani and C Behrens and S Dorr and H D Gerber and R Benazza and O Hernandez-Alba and S Cianferani and G Klebe and A Heine and K Reuter},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35815944},

doi = {10.1021/acschembio.2c00368},

issn = {1554-8937 (Electronic) 1554-8929 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {ACS Chem Biol},

abstract = {In tRNA(Asp), tRNA(Asn), tRNA(Tyr), and tRNA(His) of most bacteria and eukaryotes, the anticodon wobble position may be occupied by the modified nucleoside queuosine, which affects the speed and the accuracy of translation. Since eukaryotes are not able to synthesize queuosine de novo, they have to salvage queuine (the queuosine base) as a micronutrient from food and/or the gut microbiome. The heterodimeric Zn(2+) containing enzyme tRNA-guanine transglycosylase (TGT) catalyzes the insertion of queuine into the above-named tRNAs in exchange for the genetically encoded guanine. This enzyme has attracted medical interest since it was shown to be potentially useful for the treatment of multiple sclerosis. In addition, TGT inactivation via gene knockout leads to the suppressed cell proliferation and migration of certain breast cancer cells, which may render this enzyme a potential target for the design of compounds supporting breast cancer therapy. As a prerequisite to fully exploit the medical potential of eukaryotic TGT, we have determined and analyzed a number of crystal structures of the functional murine TGT with and without bound queuine. In addition, we have investigated the importance of two residues of its non-catalytic subunit on dimer stability and determined the Michaelis-Menten parameters of murine TGT with respect to tRNA and several natural and artificial nucleobase substrates. Ultimately, on the basis of available TGT crystal structures, we provide an entirely conclusive reaction mechanism for this enzyme, which in detail explains why the TGT-catalyzed insertion of some nucleobases into tRNA occurs reversibly while that of others is irreversible.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Torres2022b,

title = {Repeated Exposure of Macrophages to Synthetic Amorphous Silica Induces Adaptive Proteome Changes and a Moderate Cell Activation},

author = {A Torres and V Collin-Faure and H Diemer and C Moriscot and D Fenel and B Gallet and S Cianferani and J A Sergent and T Rabilloud},

url = {<Go to ISI>://WOS:000795447400001},

doi = {ARTN 1424 10.3390/nano12091424},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nanomaterials},

volume = {12},

issue = {9},

abstract = {Synthetic amorphous silica (SAS) is a nanomaterial used in a wide variety of applications, including the use as a food additive. Two types of SAS are commonly employed as a powder additive, precipitated silica and fumed silica. Numerous studies have investigated the effects of synthetic amorphous silica on mammalian cells. However, most of them have used an exposure scheme based on a single dose of SAS. In this study, we have used instead a repeated 10-day exposure scheme in an effort to better simulate the occupational exposure encountered in daily life by consumers and workers. As a biological model, we have used the murine macrophage cell line J774A.1, as macrophages are very important innate immune cells in the response to particulate materials. In order to obtain a better appraisal of the macrophage responses to this repeated exposure to SAS, we have used proteomics as a wide-scale approach. Furthermore, some of the biological pathways detected as modulated by the exposure to SAS by the proteomic experiments have been validated through targeted experiments. Overall, proteomics showed that precipitated SAS induced a more important macrophage response than fumed SAS at equal dose. Nevertheless, validation experiments showed that most of the responses detected by proteomics are indeed adaptive, as the cellular homeostasis appeared to be maintained at the end of the exposure. For example, the intracellular glutathione levels or the mitochondrial transmembrane potential at the end of the 10 days exposure were similar for SAS-exposed cells and for unexposed cells. Similarly, no gross lysosomal damage was observed after repeated exposure to SAS. Nevertheless, important functions of macrophages such as phagocytosis, TNF alpha, and interleukin-6 secretion were up-modulated after exposure, as was the expression of important membrane proteins such as the scavenger receptors, MHC-II, or the MAC-1 receptor. These results suggest that repeated exposure to low doses of SAS slightly modulates the immune functions of macrophages, which may alter the homeostasis of the immune system.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bergamelli2022b,

title = {Human Cytomegalovirus Modifies Placental Small Extracellular Vesicle Composition to Enhance Infection of Fetal Neural Cells In Vitro},

author = {M Bergamelli and H Martin and Y Aubert and J M Mansuy and M Marcellin and O Burlet-Schiltz and I Hurbain and G Raposo and J Izopet and T Fournier and A Benchoua and M Benard and M Groussolles and G Cartron and Y Tanguy Le Gac and N Moinard and G D'Angelo and C E Malnou},

doi = {10.3390/v14092030},

issn = {1999-4915 (Electronic) 1999-4915 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Viruses},

volume = {14},

issue = {9},

abstract = {Although placental small extracellular vesicles (sEVs) are extensively studied in the context of pregnancy, little is known about their role during viral congenital infection, especially at the beginning of pregnancy. In this study, we examined the consequences of human cytomegalovirus (hCMV) infection on sEVs production, composition, and function using an immortalized human cytotrophoblast cell line derived from first trimester placenta. By combining complementary approaches of biochemistry, electron microscopy, and quantitative proteomic analysis, we showed that hCMV infection increases the yield of sEVs produced by cytotrophoblasts and modifies their protein content towards a potential proviral phenotype. We further demonstrate that sEVs secreted by hCMV-infected cytotrophoblasts potentiate infection in naive recipient cells of fetal origin, including human neural stem cells. Importantly, these functional consequences are also observed with sEVs prepared from an ex vivo model of infected histocultures from early placenta. Based on these findings, we propose that placental sEVs could be important actors favoring viral dissemination to the fetal brain during hCMV congenital infection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bon2022b,

title = {Solution structure of the type I polyketide synthase Pks13 from Mycobacterium tuberculosis},

author = {C Bon and S Cabantous and S Julien and V Guillet and C Chalut and J Rima and Y Brison and W Malaga and A Sanchez-Dafun and S Gavalda and A Quemard and J Marcoux and G S Waldo and C Guilhot and L Mourey},

doi = {10.1186/s12915-022-01337-9},

issn = {1741-7007 (Electronic) 1741-7007 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {BMC Biol},

volume = {20},

issue = {1},

pages = {147},

abstract = {BACKGROUND: Type I polyketide synthases (PKSs) are multifunctional enzymes responsible for the biosynthesis of a group of diverse natural compounds with biotechnological and pharmaceutical interest called polyketides. The diversity of polyketides is impressive despite the limited set of catalytic domains used by PKSs for biosynthesis, leading to considerable interest in deciphering their structure-function relationships, which is challenging due to high intrinsic flexibility. Among nineteen polyketide synthases encoded by the genome of Mycobacterium tuberculosis, Pks13 is the condensase required for the final condensation step of two long acyl chains in the biosynthetic pathway of mycolic acids, essential components of the cell envelope of Corynebacterineae species. It has been validated as a promising druggable target and knowledge of its structure is essential to speed up drug discovery to fight against tuberculosis. RESULTS: We report here a quasi-atomic model of Pks13 obtained using small-angle X-ray scattering of the entire protein and various molecular subspecies combined with known high-resolution structures of Pks13 domains or structural homologues. As a comparison, the low-resolution structures of two other mycobacterial polyketide synthases, Mas and PpsA from Mycobacterium bovis BCG, are also presented. This study highlights a monomeric and elongated state of the enzyme with the apo- and holo-forms being identical at the resolution probed. Catalytic domains are segregated into two parts, which correspond to the condensation reaction per se and to the release of the product, a pivot for the enzyme flexibility being at the interface. The two acyl carrier protein domains are found at opposite sides of the ketosynthase domain and display distinct characteristics in terms of flexibility. CONCLUSIONS: The Pks13 model reported here provides the first structural information on the molecular mechanism of this complex enzyme and opens up new perspectives to develop inhibitors that target the interactions with its enzymatic partners or between catalytic domains within Pks13 itself.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bonhoure2022b,

title = {Extracellular 20S proteasome secreted via microvesicles can degrade poorly folded proteins and inhibit Galectin-3 agglutination activity},

author = {A Bonhoure and L Henry and C Bich and L Blanc and B Bergeret and M P Bousquet and O Coux and P E Stoebner and M Vidal},

doi = {10.1111/tra.12840},

issn = {1600-0854 (Electronic) 1398-9219 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Traffic},

volume = {23},

issue = {5},

pages = {287-304},

abstract = {Proteasomes are major non-lysosomal proteolytic complexes localized in the cytoplasm and in the nucleus of eukaryotic cells. Strikingly, high levels of extracellular proteasome have also been evidenced in the plasma (p-proteasome) of patients with specific diseases. Here, we examined the process by which proteasomes are secreted, as well as their structural and functional features once in the extracellular space. We demonstrate that assembled 20S core particles are secreted by cells within microvesicles budding from the plasma membrane. Part of the extracellular proteasome pool is also free of membranes in the supernatant of cultured cells, and likely originates from microvesicles leakage. We further demonstrate that this free proteasome released by cells (cc-proteasome for cell culture proteasome) possesses latent proteolytic activity and can degrade various extracellular proteins. Both standard (no immune-subunits) and intermediate (containing some immune-subunits) forms of 20S are observed. Moreover, we show that galectin-3, which displays a highly disordered N-terminal region, is efficiently cleaved by purified cc-proteasome, without SDS activation, likely after its binding to PSMA3 (alpha7) subunit through its intrinsically disordered region. As a consequence, galectin-3 is unable to induce red blood cells agglutination when preincubated with cc-proteasome. These results highlight potential novel physio- and pathologic functions for the extracellular proteasome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dafun2022b,

title = {Structural mass spectrometry of membrane proteins},

author = {A S Dafun and J Marcoux},

doi = {10.1016/j.bbapap.2022.140813},

issn = {1878-1454 (Electronic) 1570-9639 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Biochim Biophys Acta Proteins Proteom},

volume = {1870},

issue = {8},

pages = {140813},

abstract = {The analysis of proteins and protein complexes by mass spectrometry (MS) has come a long way since the invention of electrospray ionization (ESI) in the mid 80s. Originally used to characterize small soluble polypeptide chains, MS has progressively evolved over the past 3 decades towards the analysis of samples of ever increasing heterogeneity and complexity, while the instruments have become more and more sensitive and resolutive. The proofs of concepts and first examples of most structural MS methods appeared in the early 90s. However, their application to membrane proteins, key targets in the biopharma industry, is more recent. Nowadays, a wealth of information can be gathered from such MS-based methods, on all aspects of membrane protein structure: sequencing (and more precisely proteoform characterization), but also stoichiometry, non-covalent ligand binding (metals, drug, lipids, carbohydrates), conformations, dynamics and distance restraints for modelling. In this review, we present the concept and some historical and more recent applications on membrane proteins, for the major structural MS methods.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Demange2022b,

title = {SDR enzymes oxidize specific lipidic alkynylcarbinols into cytotoxic protein-reactive species},

author = {P Demange and E Joly and J Marcoux and P R A Zanon and D Listunov and P Rulliere and C Barthes and C Noirot and J B Izquierdo and A Rozie and K Pradines and R Hee and M V Brito and M Marcellin and R F Serre and O Bouchez and O Burlet-Schiltz and M C F Oliveira and S Ballereau and V Bernardes-Genisson and V Maraval and P Calsou and S M Hacker and Y Genisson and R Chauvin and S Britton},

doi = {10.7554/eLife.73913},

issn = {2050-084X (Electronic) 2050-084X (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Elife},

volume = {11},

abstract = {Hundreds of cytotoxic natural or synthetic lipidic compounds contain chiral alkynylcarbinol motifs, but the mechanism of action of those potential therapeutic agents remains unknown. Using a genetic screen in haploid human cells, we discovered that the enantiospecific cytotoxicity of numerous terminal alkynylcarbinols, including the highly cytotoxic dialkynylcarbinols, involves a bioactivation by HSD17B11, a short-chain dehydrogenase/reductase (SDR) known to oxidize the C-17 carbinol center of androstan-3-alpha,17-beta-diol to the corresponding ketone. A similar oxidation of dialkynylcarbinols generates dialkynylketones, that we characterize as highly protein-reactive electrophiles. We established that, once bioactivated in cells, the dialkynylcarbinols covalently modify several proteins involved in protein-quality control mechanisms, resulting in their lipoxidation on cysteines and lysines through Michael addition. For some proteins, this triggers their association to cellular membranes and results in endoplasmic reticulum stress, unfolded protein response activation, ubiquitin-proteasome system inhibition and cell death by apoptosis. Finally, as a proof-of-concept, we show that generic lipidic alkynylcarbinols can be devised to be bioactivated by other SDRs, including human RDH11 and HPGD/15-PGDH. Given that the SDR superfamily is one of the largest and most ubiquitous, this unique cytotoxic mechanism-of-action could be widely exploited to treat diseases, in particular cancer, through the design of tailored prodrugs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Godet2022b,

title = {Long non-coding RNA Neat1 and paraspeckle components are translational regulators in hypoxia},

author = {A C Godet and E Roussel and F David and F Hantelys and F Morfoisse and J Alves and F Pujol and I Ader and E Bertrand and O Burlet-Schiltz and C Froment and A K Henras and P Vitali and E Lacazette and F Tatin and B Garmy-Susini and A C Prats},

doi = {10.7554/eLife.69162},

issn = {2050-084X (Electronic) 2050-084X (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Elife},

volume = {11},

abstract = {Internal ribosome entry sites (IRESs) drive translation initiation during stress. In response to hypoxia, (lymph)angiogenic factors responsible for tissue revascularization in ischemic diseases are induced by the IRES-dependent mechanism. Here, we searched for IRES trans-acting factors (ITAFs) active in early hypoxia in mouse cardiomyocytes. Using knock-down and proteomics approaches, we show a link between a stressed-induced nuclear body, the paraspeckle, and IRES-dependent translation. Furthermore, smiFISH experiments demonstrate the recruitment of IRES-containing mRNA into paraspeckle during hypoxia. Our data reveal that the long non-coding RNA Neat1, an essential paraspeckle component, is a key translational regulator, active on IRESs of (lymph)angiogenic and cardioprotective factor mRNAs. In addition, paraspeckle proteins p54(nrb) and PSPC1 as well as nucleolin and RPS2, two p54(nrb)-interacting proteins identified by mass spectrometry, are ITAFs for IRES subgroups. Paraspeckle thus appears as a platform to recruit IRES-containing mRNAs and possibly host IRESome assembly. Polysome PCR array shows that Neat1 isoforms regulate IRES-dependent translation and, more widely, translation of mRNAs involved in stress response.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {A Mycobacterium tuberculosis fingerprint in human breath allows tuberculosis detection},

author = {S F Mosquera-Restrepo and S Zuberogoitia and L Gouxette and E Layre and M Gilleron and A Stella and D Rengel and O Burlet-Schiltz and A C Caro and L F Garcia and C Segura and C A Pelaez Jaramillo and M Rojas and J Nigou},

doi = {10.1038/s41467-022-35453-5},

issn = {2041-1723 (Electronic) 2041-1723 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nat Commun},

volume = {13},

issue = {1},

pages = {7751},

abstract = {An estimated one-third of tuberculosis (TB) cases go undiagnosed or unreported. Sputum samples, widely used for TB diagnosis, are inefficient at detecting infection in children and paucibacillary patients. Indeed, developing point-of-care biomarker-based diagnostics that are not sputum-based is a major priority for the WHO. Here, in a proof-of-concept study, we tested whether pulmonary TB can be detected by analyzing patient exhaled breath condensate (EBC) samples. We find that the presence of Mycobacterium tuberculosis (Mtb)-specific lipids, lipoarabinomannan lipoglycan, and proteins in EBCs can efficiently differentiate baseline TB patients from controls. We used EBCs to track the longitudinal effects of antibiotic treatment in pediatric TB patients. In addition, Mtb lipoarabinomannan and lipids were structurally distinct in EBCs compared to ex vivo cultured bacteria, revealing specific metabolic and biochemical states of Mtb in the human lung. This provides essential information for the rational development or improvement of diagnostic antibodies, vaccines and therapeutic drugs. Our data collectively indicate that EBC analysis can potentially facilitate clinical diagnosis of TB across patient populations and monitor treatment efficacy. This affordable, rapid and non-invasive approach seems superior to sputum assays and has the potential to be implemented at point-of-care.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Personnaz2022b,

title = {Nuclear HMGB1 protects from nonalcoholic fatty liver disease through negative regulation of liver X receptor},

author = {J Personnaz and E Piccolo and A Dortignac and J S Iacovoni and J Mariette and V Rocher and A Polizzi and A Batut and S Deleruyelle and L Bourdens and O Delos and L Combes-Soia and R Paccoud and E Moreau and F Martins and T Clouaire and F Benhamed and A Montagner and W Wahli and R F Schwabe and A Yart and I Castan-Laurell and J Bertrand-Michel and O Burlet-Schiltz and C Postic and P D Denechaud and C Moro and G Legube and C H Lee and H Guillou and P Valet and C Dray and J P Pradere},

doi = {10.1126/sciadv.abg9055},

issn = {2375-2548 (Electronic) 2375-2548 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Sci Adv},

volume = {8},

issue = {12},

pages = {eabg9055},

abstract = {Dysregulations of lipid metabolism in the liver may trigger steatosis progression, leading to potentially severe clinical consequences such as nonalcoholic fatty liver diseases (NAFLDs). Molecular mechanisms underlying liver lipogenesis are very complex and fine-tuned by chromatin dynamics and multiple key transcription factors. Here, we demonstrate that the nuclear factor HMGB1 acts as a strong repressor of liver lipogenesis. Mice with liver-specific Hmgb1 deficiency display exacerbated liver steatosis, while Hmgb1-overexpressing mice exhibited a protection from fatty liver progression when subjected to nutritional stress. Global transcriptome and functional analysis revealed that the deletion of Hmgb1 gene enhances LXRalpha and PPARgamma activity. HMGB1 repression is not mediated through nucleosome landscape reorganization but rather via a preferential DNA occupation in a region carrying genes regulated by LXRalpha and PPARgamma. Together, these findings suggest that hepatocellular HMGB1 protects from liver steatosis development. HMGB1 may constitute a new attractive option to therapeutically target the LXRalpha-PPARgamma axis during NAFLD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {A comprehensive LFQ benchmark dataset on modern day acquisition strategies in proteomics},

author = {B Van Puyvelde and S Daled and S Willems and R Gabriels and A Peredo and K Chaoui and E Mouton-Barbosa and D Bouyssie and K Boonen and C J Hughes and L A Gethings and Y Perez-Riverol and N Bloomfield and S Tate and O Schiltz and L Martens and D Deforce and M Dhaenens},

doi = {10.1038/s41597-022-01216-6},

issn = {2052-4463 (Electronic) 2052-4463 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Sci Data},

volume = {9},

issue = {1},

pages = {126},

abstract = {In the last decade, a revolution in liquid chromatography-mass spectrometry (LC-MS) based proteomics was unfolded with the introduction of dozens of novel instruments that incorporate additional data dimensions through innovative acquisition methodologies, in turn inspiring specialized data analysis pipelines. Simultaneously, a growing number of proteomics datasets have been made publicly available through data repositories such as ProteomeXchange, Zenodo and Skyline Panorama. However, developing algorithms to mine this data and assessing the performance on different platforms is currently hampered by the lack of a single benchmark experimental design. Therefore, we acquired a hybrid proteome mixture on different instrument platforms and in all currently available families of data acquisition. Here, we present a comprehensive Data-Dependent and Data-Independent Acquisition (DDA/DIA) dataset acquired using several of the most commonly used current day instrumental platforms. The dataset consists of over 700 LC-MS runs, including adequate replicates allowing robust statistics and covering over nearly 10 different data formats, including scanning quadrupole and ion mobility enabled acquisitions. Datasets are available via ProteomeXchange (PXD028735).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Javed2022b,

title = {Structural Insights into the Catalytic Cycle of a Bacterial Multidrug ABC Efflux Pump},

author = {W Javed and S Vallet and M P Clement and A Le Roy and M Moulin and M Hartlein and C Breyton and O Burlet-Schiltz and J Marcoux and C Orelle and C Ebel and A Martel and J M Jault},

doi = {10.1016/j.jmb.2022.167541},

issn = {1089-8638 (Electronic) 0022-2836 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {J Mol Biol},

volume = {434},

issue = {9},

pages = {167541},

abstract = {ABC ("ATP-Binding Cassette") transporters of the type IV subfamily consist of exporters involved in the efflux of many compounds, notably those capable to confer multidrug resistance like the mammalian P-glycoprotein or the bacterial transporter BmrA. They function according to an alternating access mechanism between inward-facing (IF) and outward-facing (OF) conformations, but the extent of physical separation between the two nucleotide-binding domains (NBDs) in different states is still unsettled. Small Angle Neutron Scattering and hydrogen/deuterium exchange coupled to mass spectrometry were used to highlight different conformational states of BmrA during its ATPase cycle. In particular, mutation of the conserved Lysine residue of the Walker-A motif (K380A) captures BmrA in an ATP-bound IF conformation prior to NBD closure. While in the transition-like state induced by vanadate wild-type BmrA is mainly in an OF conformation, the transporter populates only IF conformations in either the apo state or in the presence of ADP/Mg. Importantly, in this post-hydrolytic step, distances between the two NBDs of BmrA seem to be more separated than in the apo state, but they remain shorter than the widest opening found in the related MsbA transporter. Overall, our results highlight the main steps of the catalytic cycle of a homodimeric bacterial multidrug transporter and underline structural and functional commonalities as well as oddities among the type IV subfamily of ABC transporters.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nyonda2022b,

title = {N-acetylation of secreted proteins in Apicomplexa is widespread and is independent of the ER acetyl-CoA transporter AT1},

author = {Mary Akinyi Nyonda and Jean-Baptiste Boyer and Lucid Belmudes and Aarti Krishnan and Paco Pino and Yohann Couté and Mathieu Brochet and Thierry Meinnel and Dominique Soldati-Favre and Carmela Giglione},

doi = {10.1242/jcs.259811},

issn = {1477-9137},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Journal of Cell Science},

volume = {135},

issue = {15},

pages = {jcs259811},

abstract = {Acetyl-CoA participates in post-translational modification of proteins and in central carbon and lipid metabolism in several cell compartments. In mammals, acetyl-CoA transporter 1 (AT1, also known as SLC33A1) facilitates the flux of cytosolic acetyl-CoA into the endoplasmic reticulum (ER), enabling the acetylation of proteins of the secretory pathway, in concert with the activity of dedicated acetyltransferases such as NAT8. However, the involvement of the ER acetyl-CoA pool in acetylation of ER-transiting proteins in Apicomplexa is unknown. Here, we identified homologs of AT1 and NAT8 in Toxoplasma gondii and Plasmodium berghei parasites. Proteome-wide analyses revealed widespread N-terminal acetylation of secreted proteins in both species. Such extensive acetylation of N-terminally processed proteins has not been observed previously in any other organism. Deletion of AT1 homologs in both T. gondii and P. berghei resulted in considerable reductions in parasite fitness. In P. berghei, AT1 was found to be important for growth of asexual blood stages, production of female gametocytes and male gametocytogenesis, implying its requirement for parasite transmission. In the absence of AT1, lysine acetylation and N-terminal acetylation in T. gondii remained globally unaltered, suggesting an uncoupling between the role of AT1 in development and active acetylation occurring along the secretory pathway.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Job2022b,

title = {Genomic erosion and horizontal gene transfer shape functional differences of the ExlA toxin in Pseudomonas spp},

author = {Viviana Job and Laura Gomez-Valero and Adèle Renier and Christophe Rusniok and Stephanie Bouillot and Viviane Chenal-Francisque and Erwan Gueguen and Annie Adrait and Mylène Robert-Genthon and Katy Jeannot and Peter Panchev and Sylvie Elsen and Marie-Odile Fauvarque and Yohann Couté and Carmen Buchrieser and Ina Attrée},

doi = {10.1016/j.isci.2022.104596},

issn = {2589-0042},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {iScience},

volume = {25},

issue = {7},

pages = {104596},

abstract = {Two-partner secretion (TPS) is widespread in the bacterial world. The pore-forming TPS toxin ExlA of Pseudomonas aeruginosa is conserved in pathogenic and environmental Pseudomonas. While P. chlororaphis and P. entomophila displayed ExlA-dependent killing, P. putida did not cause damage to eukaryotic cells. ExlA proteins interacted with epithelial cell membranes; however, only ExlA Pch induced the cleavage of the adhesive molecule E-cadherin. ExlA proteins participated in insecticidal activity toward the larvae of Galleria mellonella and the fly Drosophila melanogaster. Evolutionary analyses demonstrated that the differences in the C-terminal domains are partly due to horizontal movements of the operon within the genus Pseudomonas. Reconstruction of the evolutionary history revealed the complex horizontal acquisitions. Together, our results provide evidence that conserved TPS toxins in environmental Pseudomonas play a role in bacteria-insect interactions and discrete differences in CTDs may determine their specificity and mode of action toward eukaryotic cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Swale2022b,

title = {Altiratinib blocks Toxoplasma gondii and Plasmodium falciparum development by selectively targeting a spliceosome kinase},

author = {Christopher Swale and Valeria Bellini and Matthew W Bowler and Nardella Flore and Marie-Pierre Brenier-Pinchart and Dominique Cannella and Lucid Belmudes and Caroline Mas and Yohann Couté and Fabrice Laurent and Artur Scherf and Alexandre Bougdour and Mohamed-Ali Hakimi},

url = {https://www.science.org/doi/10.1126/scitranslmed.abn3231},

doi = {10.1126/scitranslmed.abn3231},

issn = {1946-6234, 1946-6242},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Science Translational Medicine},

volume = {14},

issue = {656},

pages = {eabn3231},

abstract = {The Apicomplexa comprise a large phylum of single-celled, obligate intracellular protozoa that include Toxoplasma gondii , Plasmodium , and Cryptosporidium spp., which infect humans and animals and cause severe parasitic diseases. Available therapeutics against these diseases are limited by suboptimal efficacy and frequent side effects, as well as the emergence and spread of resistance. We use a drug repurposing strategy and identify altiratinib, a compound originally developed to treat glioblastoma, as a promising drug candidate with broad spectrum activity against apicomplexans. Altiratinib is parasiticidal and blocks the development of intracellular zoites in the nanomolar range and with a high selectivity index when used against T. gondii . We have identified Tg PRP4K of T. gondii as the primary target of altiratinib using genetic target deconvolution, which highlighted key residues within the kinase catalytic site that conferred drug resistance when mutated. We have further elucidated the molecular basis of the inhibitory mechanism and species selectivity of altiratinib for Tg PRP4K and for its Plasmodium falciparum counterpart, Pf CLK3. Our data identified structural features critical for binding of the other Pf CLK3 inhibitor, TCMDC-135051. Consistent with the splicing control activity of this kinase family, we have shown that altiratinib can cause global disruption of splicing, primarily through intron retention in both T. gondii and P. falciparum . Thus, our data establish parasitic PRP4K/CLK3 as a potential pan-apicomplexan target whose repertoire of inhibitors can be expanded by the addition of altiratinib. , Spliceosome targeting by altiratinib leads to Toxoplasma and Plasmodium inhibition. , Repurposing against parasites Toxoplasma gondii and Plasmodium falciparum are members of the Apicomplexa phylum of parasitic protists that can cause severe infections in humans and other animals. Available drugs against these parasites have limited efficacy and undesirable side effects. Swale et al. used a drug repurposing screen and identified altiratinib as a potential antiparasitic drug. Altiratinib was originally developed as a drug to treat glioblastoma, and, here, they show that this drug has potent parasiticidal activation against T. gondii . Through drug resistance screening and genetic target deconvolution, Tg PRP4K of T. gondii was identified as the primary target of altiratinib, which was confirmed for its counterpart in P. falciparum , Pf CLK3. Altiratinib was shown to globally disrupt splicing by targeting this family of parasite kinases. These findings support further development of pan-apicomplexan inhibitors that target this pathway.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mladenov2022b,

title = {Proteomics Evidence of a Systemic Response to Desiccation in the Resurrection Plant Haberlea rhodopensis},

author = {Petko Mladenov and Diana Zasheva and Sébastien Planchon and Céline C Leclercq and Denis Falconet and Lucas Moyet and Sabine Brugière and Daniela Moyankova and Magdalena Tchorbadjieva and Myriam Ferro and Norbert Rolland and Jenny Renaut and Dimitar Djilianov and Xin Deng},

url = {https://www.mdpi.com/1422-0067/23/15/8520},

doi = {10.3390/ijms23158520},

issn = {1422-0067},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

issue = {15},

pages = {8520},

abstract = {Global warming and drought stress are expected to have a negative impact on agricultural productivity. Desiccation-tolerant species, which are able to tolerate the almost complete desiccation of their vegetative tissues, are appropriate models to study extreme drought tolerance and identify novel approaches to improve the resistance of crops to drought stress. In the present study, to better understand what makes resurrection plants extremely tolerant to drought, we performed transmission electron microscopy and integrative large-scale proteomics, including organellar and phosphorylation proteomics, and combined these investigations with previously published transcriptomic and metabolomics data from the resurrection plant Haberlea rhodopensis. The results revealed new evidence about organelle and cell preservation, posttranscriptional and posttranslational regulation, photosynthesis, primary metabolism, autophagy, and cell death in response to desiccation in H. rhodopensis. Different protective intrinsically disordered proteins, such as late embryogenesis abundant (LEA) proteins, thaumatin-like proteins (TLPs), and heat shock proteins (HSPs), were detected. We also found a constitutively abundant dehydrin in H. rhodopensis whose phosphorylation levels increased under stress in the chloroplast fraction. This integrative multi-omics analysis revealed a systemic response to desiccation in H. rhodopensis and certain targets for further genomic and evolutionary studies on DT mechanisms and genetic engineering towards the improvement of drought tolerance in crops.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Direct visualization of pre-protamine 2 detects protamine assembly failures and predicts ICSI success},

author = {Maryam Rezaei-Gazik and Alexandra Vargas and Amir Amiri-Yekta and Anne-Laure Vitte and Arvand Akbari and Sophie Barral and Vahid Esmaeili and Florent Chuffart and Mohammad Ali Sadighi-Gilani and Yohann Couté and Poopak Eftekhari-Yazdi and Saadi Khochbin and Sophie Rousseaux and Mehdi Totonchi},

url = {https://academic.oup.com/molehr/article/doi/10.1093/molehr/gaac004/6527641},

doi = {10.1093/molehr/gaac004},

issn = {1360-9947, 1460-2407},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Molecular Human Reproduction},

volume = {28},

issue = {2},

pages = {gaac004},

abstract = {Abstract Histone-to-protamine transition is an essential step in the generation of fully functional spermatozoa in various mammalian species. In human and mouse, one of the two protamine-encoding genes produces a precursor pre-protamine 2 (pre-PRM2) protein, which is then processed and assembled. Here, we design an original approach based on the generation of pre-PRM2-specific antibodies to visualize the unprocessed pre-PRM2 by microscopy, flow cytometry and immunoblotting. Using mouse models with characterized failures in histone-to-protamine replacement, we show that pre-PRM2 retention is tightly linked to impaired nucleosome disassembly. Additionally, in elongating/condensing spermatids, we observe that pre-PRM2 and transition protein are co-expressed spatiotemporally, and their physical interaction suggests that these proteins act simultaneously rather than successively during histone replacement. By using our anti-human pre-PRM2 antibody, we also measured pre-PRM2 retention rates in the spermatozoa from 49 men of a series of infertile couples undergoing ICSI, which shed new light on the debated relation between pre-PRM2 retention and sperm parameters. Finally, by monitoring 2-pronuclei embryo formation following ICSI, we evaluated the fertilization ability of the sperm in these 49 patients. Our results suggest that the extent of pre-PRM2 retention in sperm, rather than pre-PRM2 accumulation per se, is associated with fertilization failure. Hence, anti-pre-PRM2 antibodies are valuable tools that could be used in routine monitoring of sperm parameters in fertility clinics, as well as in experimental research programmes to better understand the obscure process of histone-to-protamine transition.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gfrerer2022b,

title = {A Micrarchaeon Isolate Is Covered by a Proteinaceous S-Layer},

author = {Sabrina Gfrerer and Dennis Winkler and Julia Novion Ducassou and Yohann Couté and Reinhard Rachel and Johannes Gescher},

editor = {Nicole R Buan},

url = {https://journals.asm.org/doi/10.1128/aem.01553-21},

doi = {10.1128/aem.01553-21},

issn = {0099-2240, 1098-5336},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Applied and Environmental Microbiology},

volume = {88},

issue = {5},

pages = {e01553–21},

abstract = {Our knowledge about the DPANN superphylum, which comprises several archaeal phyla with limited metabolic capacities, is mostly based on genomic data derived from cultivation-independent approaches. This study examined the surface structure of a recently cultivated member “ Candidatus Micrarchaeum harzensis A_DKE,” an archaeal symbiont dependent on an interaction with a host organism for growth. , ABSTRACT In previous publications, it was hypothesized that Micrarchaeota cells are covered by two individual membrane systems. This study proves that at least the recently cultivated “ Candidatus Micrarchaeum harzensis A_DKE” possesses an S-layer covering its cytoplasmic membrane. The potential S-layer protein was found to be among the proteins with the highest abundance in “ Ca. Micrarchaeum harzensis A_DKE,” and in silico characterization of its primary structure indicated homologies to other known S-layer proteins. Homologues of this protein were found in other Micrarchaeota genomes, which raises the question of whether the ability to form an S-layer is a common trait within this phylum. The S-layer protein seems to be glycosylated, and the micrarchaeon expresses genes for N-glycosylation under cultivation conditions, despite not being able to synthesize carbohydrates. Electron micrographs of freeze-etched samples of a previously described coculture, containing “ Ca. Micrarchaeum harzensis A_DKE” and a Thermoplasmatales member as its host organism, verified the hypothesis of an S-layer on the surface of “ Ca. Micrarchaeum harzensis A_DKE.” Both organisms are clearly distinguishable by cell size, shape, and surface structure. IMPORTANCE Our knowledge about the DPANN superphylum, which comprises several archaeal phyla with limited metabolic capacities, is mostly based on genomic data derived from cultivation-independent approaches. This study examined the surface structure of a recently cultivated member “ Candidatus Micrarchaeum harzensis A_DKE,” an archaeal symbiont dependent on an interaction with a host organism for growth. The interaction requires direct cell contact between interaction partners, a mechanism which is also described for other DPANN archaea. Investigating the surface structure of “ Ca. Micrarchaeum harzensis A_DKE” is an important step toward understanding the interaction between Micrarchaeota and their host organisms and living with limited metabolic capabilities, a trait shared by several DPANN archaea.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vigetti2022b,

title = {The BCC7 Protein Contributes to the Toxoplasma Basal Pole by Interfacing between the MyoC Motor and the IMC Membrane Network},

author = {Luis Vigetti and Tatiana Labouré and Chloé Roumégous and Dominique Cannella and Bastien Touquet and Claudine Mayer and Yohann Couté and Karine Frénal and Isabelle Tardieux and Patricia Renesto},

url = {https://www.mdpi.com/1422-0067/23/11/5995},

doi = {10.3390/ijms23115995},

issn = {1422-0067},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

issue = {11},

pages = {5995},

abstract = {T. gondii is a eukaryotic parasite that has evolved a stage called tachyzoite which multiplies in host cells by producing two daughter cells internally. These nascent tachyzoites bud off their mother and repeat the division process until the expanding progenies escape to settle and multiply in other host cells. Over these intra- and extra-cellular phases, the tachyzoite maintains an essential apicobasal polarity that emerges through a unique bidirectional budding process of the elongating cells. This process requires the assembly of several molecular complexes that, at the nascent pole, encompass structural and myosin motor elements. To characterize a recently identified basal pole marker named BCC7 with respect to the posterior myosin J and myosin C motors, we used conventional biochemistry as well as advanced proteomic and in silico analysis in conjunction with live and super resolution microscopy of transgenic fluorescent tachyzoites. We document that BCC7 forms a ribbed ring below which myosin C motor entities distribute regularly. In addition, we identified—among 13 BCC7 putative partners—two novel and five known members of the inner membrane complex (IMC) family which ends at the apical side of the ring. Therefore, BCC7 could assist the stabilization of the IMC plaques and contribute to the parasite biomechanical properties.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Environmental cues from neural crest derivatives act as metastatic triggers in an embryonic neuroblastoma model},

author = {Dounia Ben Amar and Karine Thoinet and Benjamin Villalard and Olivier Imbaud and Clélia Costechareyre and Loraine Jarrosson and Florie Reynaud and Julia Novion Ducassou and Yohann Couté and Jean-François Brunet and Valérie Combaret and Nadège Corradini and Céline Delloye-Bourgeois and Valérie Castellani},

doi = {10.1038/s41467-022-30237-3},

issn = {2041-1723},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nature Communications},

volume = {13},

issue = {1},

pages = {2549},

abstract = {Embryonic malignant transformation is concomitant to organogenesis, often affecting multipotent and migratory progenitors. While lineage relationships between malignant cells and their physiological counterparts are extensively investigated, the contribution of exogenous embryonic signals is not fully known. Neuroblastoma (NB) is a childhood malignancy of the peripheral nervous system arising from the embryonic trunk neural crest (NC) and characterized by heterogeneous and interconvertible tumor cell identities. Here, using experimental models mimicking the embryonic context coupled to proteomic and transcriptomic analyses, we show that signals released by embryonic sympathetic ganglia, including Olfactomedin-1, induce NB cells to shift from a noradrenergic to mesenchymal identity, and to activate a gene program promoting NB metastatic onset and dissemination. From this gene program, we extract a core signature specifically shared by metastatic cancers with NC origin. This reveals non-cell autonomous embryonic contributions regulating the plasticity of NB identities and setting pro-dissemination gene programs common to NC-derived cancers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dragic2022b,

title = {The hexosamine pathway and coat complex II promote malignant adaptation to nutrient scarcity},

author = {Helena Dragic and Audrey Barthelaix and Cédric Duret and Simon Le Goupil and Hadrien Laprade and Sophie Martin and Sabine Brugière and Yohann Couté and Christelle Machon and Jerome Guitton and Justine Rudewicz and Paul Hofman and Serge Lebecque and Cedric Chaveroux and Carole Ferraro-Peyret and Toufic Renno and Serge N Manié},

doi = {10.26508/lsa.202101334},

issn = {2575-1077},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Life Science Alliance},

volume = {5},

issue = {7},

pages = {e202101334},

abstract = {The glucose-requiring hexosamine biosynthetic pathway (HBP), which produces UDP-N-acetylglucosamine for glycosylation reactions, promotes lung adenocarcinoma (LUAD) progression. However, lung tumor cells often reside in low-nutrient microenvironments, and whether the HBP is involved in the adaptation of LUAD to nutrient stress is unknown. Here, we show that the HBP and the coat complex II (COPII) play a key role in cell survival during glucose shortage. HBP up-regulation withstood low glucose-induced production of proteins bearing truncated N-glycans, in the endoplasmic reticulum. This function for the HBP, alongside COPII up-regulation, rescued cell surface expression of a subset of glycoproteins. Those included the epidermal growth factor receptor (EGFR), allowing an EGFR-dependent cell survival under low glucose in anchorage-independent growth. Accordingly, high expression of the HBP rate-limiting enzyme GFAT1 was associated with wild-type EGFR activation in LUAD patient samples. Notably, HBP and COPII up-regulation distinguished LUAD from the lung squamous-cell carcinoma subtype, thus uncovering adaptive mechanisms of LUAD to their harsh microenvironment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Permiakova2022b,

title = {Sketched Stochastic Dictionary Learning for large‐scale data and application to high‐throughput mass spectrometry},

author = {Olga Permiakova and Thomas Burger},

url = {https://onlinelibrary.wiley.com/doi/10.1002/sam.11542},

doi = {10.1002/sam.11542},

issn = {1932-1864, 1932-1872},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Statistical Analysis and Data Mining: The ASA Data Science Journal},

volume = {15},

issue = {1},

pages = {43-56},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Capizzi2022b,

title = {Developmental defects in Huntington's disease show that axonal growth and microtubule reorganization require NUMA1},

author = {Mariacristina Capizzi and Rémi Carpentier and Eric Denarier and Annie Adrait and Rayane Kassem and Marina Mapelli and Yohann Couté and Sandrine Humbert},

doi = {10.1016/j.neuron.2021.10.033},

issn = {1097-4199},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Neuron},

volume = {110},

issue = {1},

pages = {36–50.e5},

abstract = {Although the classic symptoms of Huntington's disease (HD) manifest in adulthood, neural progenitor cell behavior is already abnormal by 13 weeks' gestation. To determine how these developmental defects evolve, we turned to cell and mouse models. We found that layer II/III neurons that normally connect the hemispheres are limited in their growth in HD by microtubule bundling defects within the axonal growth cone, so that fewer axons cross the corpus callosum. Proteomic analyses of the growth cones revealed that NUMA1 (nuclear/mitotic apparatus protein 1) is downregulated in HD by miR-124. Suppressing NUMA1 in wild-type cells recapitulates the microtubule and axonal growth defects of HD, whereas raising NUMA1 levels with antagomiR-124 or stabilizing microtubules with epothilone B restores microtubule organization and rescues axonal growth. NUMA1 therefore regulates the microtubule network in the growth cone, and HD, which is traditionally conceived as a disease of intracellular trafficking, also disturbs the cytoskeletal network.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}