A5001101783- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- Bacterial biofilms and quorum sensing
- Growth Hormone and Insulin-like Growth Factors
- Estrogen and related hormone effects
- Bacteriophages and microbial interactions
- Photoreceptor and optogenetics research
- Protein Kinase Regulation and GTPase Signaling
- Metabolomics and Mass Spectrometry Studies
- Angiogenesis and VEGF in Cancer
- Vibrio bacteria research studies
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Enzyme Production and Characterization
- Biotin and Related Studies
- Clostridium difficile and Clostridium perfringens research
- Receptor Mechanisms and Signaling
- Metabolism, Diabetes, and Cancer
- Pituitary Gland Disorders and Treatments
- Drug Transport and Resistance Mechanisms
- Protein Interaction Studies and Fluorescence Analysis
- Caveolin-1 and cellular processes
Centre National de la Recherche Scientifique
2015-2024
Université Paris Cité
2015-2024
Sorbonne Paris Cité
2011-2024
Cibles Thérapeutiques et conception de médicaments
1995-2023
Laboratoire de Cristallographie et RMN Biologiques
2010-2019
Délégation Paris 5
2007-2019
Sorbonne Université
2018
Observatoire de Paris
2006-2015
Utrecht University
2005
Laboratoire d'Enzymologie et Biochimie Structurales
1997-2000
Angiogenesis is tightly regulated through the binding of vascular endothelial growth factors (VEGFs) to their receptors (VEGFRs). In this context, we showed that human VEGFR1 domain 2 crystallizes in presence Zn2+, Co2+ or Cu2+ as a dimer forms via metal-ion interactions and interlocked hydrophobic surfaces. SAXS, NMR size exclusion chromatography analyses confirm formation solution Co2+, Cd2+ Cu2+. Since metal-induced dimerization masks VEGFs surface, investigated ability metal ions...
Charcot–Marie–Tooth neuropathy has been reported to be associated with renal diseases, mostly focal segmental glomerulosclerosis (FSGS). However, the common mechanisms underlying and FSGS remain unknown. Mutations in INF2 were recently identified patients autosomal dominant FSGS. encodes a formin protein that interacts Rho-GTPase CDC42 myelin lymphocyte (MAL) are implicated essential steps of myelination maintenance. We therefore hypothesized may responsible for cases
Mutation-dependent overproduction of intrinsic β-lactamase AmpC is considered the main cause resistance clinical strains Pseudomonas aeruginosa to antipseudomonal penicillins and cephalosporins. Analysis 31 AmpC-overproducing isolates exhibiting a greater ceftazidime than piperacillin-tazobactam revealed presence 17 mutations in β-lactamase, combined with various polymorphic amino acid substitutions. When overexpressed AmpC-deficient P. 4098, genes coding for 20/23 these variants were found...
Abstract Tripartite multidrug efflux systems of Gram-negative bacteria are composed an inner membrane transporter, outer channel and a periplasmic adaptor protein. They assumed to form ducts inside the periplasm facilitating drug exit across membrane. Here we present reconstitution native Pseudomonas aeruginosa MexAB–OprM Escherichia coli AcrAB–TolC tripartite Resistance Nodulation cell Division (RND) in lipid nanodisc system. Single-particle analysis by electron microscopy reveals protein...
Proteins of the Wiskott-Aldrich Syndrome protein (WASp) family connect signaling pathways to actin polymerization-driven cell motility. The ubiquitous homolog WASp, N-WASp, is a multidomain that interacts with Arp2/3 complex and G-actin via its C-terminal WA domain stimulate polymerization. activity N-WASp enhanced by binding effectors like Cdc42-guanosine 5′-3-<i>O</i>-(thio)triphosphate, phosphatidylinositol bisphosphate, or <i>Shigella</i> IcsA protein. Here we show SH3-SH2-SH3 adaptor...
Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain–lung–thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC). The objectives of the present study were (i) detection NKX2-1 in patients with CH associated pneumopathy and/or BHC, (ii) functional analysis new vitro (iii) description phenotypic spectrum syndrome. We identified three heterozygous missense (L176V, P202L, Q210P), a splice...
The recent identification of mutations in the INF2 gene, which encodes a member formin family actin-regulating proteins, cases familial FSGS supports importance an intact actin cytoskeleton podocyte function. To determine better prevalence autosomal dominant FSGS, we screened 54 families (78 patients) and detected 17% them. All were missense variants localized to N-terminal diaphanous inhibitory domain protein, region that interacts with C-terminal autoregulatory domain, thereby competing...
Constitutive overproduction of the pump MexXY-OprM is recognized as a major cause resistance to aminoglycosides, fluoroquinolones, and zwitterionic cephalosporins in Pseudomonas aeruginosa. In this study, 57 clonally unrelated strains recovered from non-cystic fibrosis patients were analyzed characterize mutations resulting upregulation mexXY operon. Forty-four (77.2%) strains, classified agrZ mutants found harbor inactivating local repressor gene (mexZ) operon (n = 33; 57.9%) or introducing...
NKX2-1 (NK2 homeobox 1) is a critical regulator of transcription for the surfactant protein (SP)-B and -C genes (SFTPB SFTPC, respectively). We identified functionally characterized two new de novo mutations c.493C>T (p.R165W) c.786_787del2 (p.L263fs) in infants with closely similar severe interstitial lung disease (ILD), hypotonia, congenital hypothyroidism. Functional analyses using A549 HeLa cells revealed that NKX2-1-p.L263fs induced neither SFTPB nor SFTPC promoter activation had...
Primary ovarian insufficiency (POI) is a disorder associated with female infertility, which affects approximately 1% of women under 40 years age. A genetic component has been suggested as one possible cause the majority cases nonsyndromic forms. Newborn Ovary Homeobox (NOBOX) an ovary-specific gene, playing critical role in ovary mice, its absence leads to sterility mimicking POI. In this study, we sequenced NOBOX cohort 178 idiopathic Among 19 identified variations, described nonsense...
Pseudomonas aeruginosa is a multi-drug-resistant human opportunistic pathogen largely involved in nosocomial infections. Unfortunately, effective antibacterial agents are lacking. Exploring its physiology at the post-translational modifications (PTMs) level may contribute to renewal of combat tactics. Recently, lysine succinylation was discovered bacteria and seems be an interesting PTM. We present first succinylome acetylome P. PA14 cultured presence four different carbon sources using 2D...
Abstract Most membrane proteins studies require the use of detergents, but because lack a general, accurate and rapid method to quantify them, many uncertainties remain that hamper proper functional structural data analyses. To solve this problem, we propose based on matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) allows quantification pure or mixed detergents in complex with proteins. We validated wide variety automated process, thereby allowing routine for...
Abstract The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting large variety of antimicrobial compounds. Crystal structures MexB and its Escherichia coli homolog AcrB had revealed asymmetric trimers depicting directional drug pathway conformational interconversion (from Loose Tight binding pockets to Open gate (LTO) for exit). It remains unclear how acquires LTO form. Here performing functional cryo-EM structural...
Antibiotic resistance is a major public health issue and many bacteria responsible for human infections have now developed variety of antibiotic mechanisms. For instance, Pseudomonas aeruginosa, disease-causing Gram-negative bacteria, resistant to almost every class antibiotics. Much this attributable multidrug efflux pumps, which are tripartite membrane protein complexes that span both membranes actively expel Here we report an in vitro procedure monitor transport by the MexAB-OprM pump. By...
Previously, we pointed out in
Competitive antagonists of the human prolactin (hPRL) receptor are a novel class molecules potential therapeutic interest in context cancer. We recently developed pure antagonist Del1-9-G129R-hPRL by deleting nine N-terminal residues G129R-hPRL, first generation partial antagonist. determined crystallographic structure Del1-9-G129R-hPRL, which revealed no major change compared with wild type hPRL, indicating that its antagonistic properties intrinsically due to mutations. To decipher...
We report the first crystal structure of a 1:2 hormone.receptor complex that involves prolactin (PRL) as ligand, at 3.8-A resolution. Stable ternary complexes were obtained by generating affinity-matured PRL variants harboring an N-terminal tail from ovine placental lactogen, closely related receptor (PRLR) ligand. This allows one to draw up exhaustive inventory residues involved PRL.PRLR site 2 interface, consistent with all previously reported site-directed mutagenesis data. propose, this...
Understanding direct salt effects on protein crystal polymorphism is addressed by comparing different forms (triclinic, monoclinic, tetragonal and orthorhombic) for hen, turkey, bob white quail human lysozymes. Four new structures of hen egg-white lysozyme are reported: crystals grown in the presence NapTS diffracted to 1.85 Å, NaI 1.6 NaNO3 1.45 Å KSCN 1.63 Å. These compared with previously published order draw a mapping surface lysozymes interacting monovalent anions, such as nitrate,...