A5059979662- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Enzyme Structure and Function
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Blood Coagulation and Thrombosis Mechanisms
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Protein Structure and Dynamics
- Asthma and respiratory diseases
- COVID-19 epidemiological studies
- Ion channel regulation and function
- Immunotherapy and Immune Responses
- Protease and Inhibitor Mechanisms
- HIV/AIDS drug development and treatment
- Monoclonal and Polyclonal Antibodies Research
- Cellular Mechanics and Interactions
- Cytokine Signaling Pathways and Interactions
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Allergic Rhinitis and Sensitization
- bioluminescence and chemiluminescence research
- HIV Research and Treatment
- Immune Response and Inflammation
Alagappa University
2025
Anna University, Chennai
2025
Institut Pasteur
2010-2024
Inserm
2020-2024
Université Paris Cité
2022-2024
La Ligue Contre le Cancer
2021-2024
Institut Pasteur du Laos
2021
Centre National de la Recherche Scientifique
1995-2020
Institut Textile et Chimique
2020
Délégation Paris 6
2019
Assessment of the cumulative incidence SARS-CoV-2 infections is critical for monitoring course and extent COVID-19 epidemic. Here, we report estimated seroprevalence in French population proportion infected individuals who developed neutralising antibodies at three points throughout first epidemic wave. Testing 11,000 residual specimens anti-SARS-CoV-2 IgG antibodies, find nationwide 0.41% (95% CI: 0.05-0.88) mid-March, 4.14% 3.31-4.99) mid-April 4.93% 4.02-5.89) mid-May 2020. Approximately...
The adenylate cyclase (CyaA) secreted by Bordetella pertussis is a toxin that able to enter eukaryotic cells and cause dramatic increase in cAMP level. In addition, the also exhibits an intrinsic hemolytic activity independent from ATP cycling catalytic of toxin. Both cytotoxic activities are calcium-dependent. this work, we have analyzed calcium interacting properties CyaA. We shown CyaA exposed CaCl2 could retain membrane binding capability when it was further assayed presence excess EGTA....
Although the COVID-19 pandemic peaked in March/April 2020 France, prevalence of infection is barely known. Using high-throughput methods, we assessed herein serological response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1847 participants working three sites an institution Paris conurbation. In May-July 2020, 11% (95% confidence interval [CI]: 9.7-12.6) serums were positive for IgG SARS-CoV-2 N and S proteins, 9.5% CI: 8.2-11.0) neutralizer pseudo-typed virus...
Abstract We describe here an extensive structure‐bioluminescence relationship study of a chemical library analogues coelenterazine, using nanoKAZ/NanoLuc, mutated luciferase originated from the catalytic subunit deep‐sea shrimp Oplophorus gracilirostris . Out 135 O‐acetylated precursors that were prepared by our recently reported synthesis and following their hydrolysis to give solutions corresponding luciferins, notable bioluminescence improvements achieved in comparison with furimazine,...
Nanofabrication by molecular self-assembly involves the design of molecules and strategies so that shape chemical complementarities drive units to organize spontaneously into desired structures. The power makes it ubiquitous strategy living organized matter provides a powerful tool chemists. However, challenging issue in complex supramolecular structures is understand how kinetically efficient pathways emerge from multitude possible transition states routes. Unfortunately, very few systems...
IL-2 and IL-15 differentially control the development, activation proliferation of human NK cells, although they share common signal-transducing receptor chains CD122 gamma. To explore this issue, we analyzed in detail kinetics cytokine expression, binding, signaling responses cells treated with gamma-chain family cytokines. We provide evidence for sequential expression IL-15Ralpha IL-2Ralpha at surface cytokine-stimulated independent used stimulation (IL-2, IL-15, or IL-7). Binding...
An original gram-scale synthesis of O-acetylated forms coelenterazine, furimazine or hydroxy-bearing analogues luciferins is described. The comparison over two hours their bioluminescence, using the nanoKAZ/NanoLuc luciferase, provides remarkable insights useful for selection a substrate adapted given application.
Adenomatous polyposis coli (APC) is a tumor suppressor whose mutations underlie familial adenomatous (FAP) and colorectal cancer. Although its role in intestinal epithelial cells well characterized, APC importance T cell biology ill defined. regulates cytoskeleton organization, polarity, migration various types. Here, we address whether plays lymphocyte migration. Using series of tools, unveiled that from FAP patients carrying display impaired adhesion motility constrained environments. We...
Abstract In addition to its procoagulant and anticoagulant roles in the blood coagulation cascade, thrombin works as a signaling molecule when it interacts with G‐protein coupled receptors PAR1, PAR3, PAR4. We have mapped epitopes responsible for these interactions using enzymatic assays Ala scanning mutagenesis. The overlap considerably, are almost identical those of fibrinogen fibrin, but few unanticipated differences uncovered that help explain higher (90‐fold) specificity PAR1 relative...
Inwardly rectifying K(+) currents are generated by a complex of four Kir (Kir1-6) subunits. Pore properties conferred the second transmembrane domain (M2) each subunit. Using cadmium ions as cysteine-interacting probe, we examined accessibility substituted cysteines in M2 Kir6.2 subunit inwardly K(ATP) channels. The ability Cd(2+) to inhibit channels was used estimate accessibility. distribution is consistent with an alpha-helical structure M2. apparent surface reactivity broad, and most...
Residue 225 in serine proteases of the chymotrypsin family is Pro or Tyr more than 95% nearly 300 available sequences. Proteases with Y225 (like some blood coagulation and complement factors) are almost exclusively found vertebrates, whereas P225 degradative enzymes) present from bacteria to human. Saturation mutagenesis thrombin shows that residue affects ligand recognition up 60,000-fold. With exception Phe, all residues associated comparable greatly reduced catalytic activity relative...
Isothermal titration calorimetry and X-ray crystallography have been used to determine the structural thermodynamic consequences associated with constraining pTyr residue of pYEEI ligand for Src Homology 2 domain kinase (Src SH2 domain). The conformationally constrained peptide mimics that were are cyclopropane-derived isosteres whereby a cyclopropane ring substitutes N-Cα-Cβ atoms phosphotyrosine. Comparison data binding relative their equivalent flexible analogues as well native...
The IL-7R alpha-chain and the common gamma-chain (gamma(c)) are both components of IL-7R. Human plasma harbors soluble forms (sIL-7Ralpha sgamma(c)) that detected assayed by Western blotting, showing levels sIL-7Ralpha higher than sgamma(c) (47.5 ng/ml 1.5 ng/ml, respectively). Gel electrophoresis tandem mass spectrometry used to analyze deglycosylated, affinity-purified protein showed is generated through differentially spliced mRNA, not membrane receptor shedding. Plasma present as...
Assessing the strength and kinetics of molecular interactions cells with extracellular matrix is fundamental to understand cell adhesion processes. Given relevance these processes, there a strong need for physical methods quantitatively assess mechanism at single-cell level, allowing discrimination different behaviors. Here we introduce acoustic force spectroscopy (scAFS), an approach that makes use waves exert controlled forces, up 1 nN, hundreds individual in parallel. We demonstrate...
Polyamines cause inward rectification of (Kir) K+ channels, but the mechanism is controversial. We employed scanning mutagenesis Kir6.2, and a structural series blocking diamines, to combinatorially examine role both channel blocker charges. find that introduced glutamates at any pore-facing residue in inner cavity, up including entrance selectivity filter, can confer strong rectification. As these negative charges are moved higher (toward filter), or lower cytoplasm), they preferentially...
Escherichia coli grown in limited methionine and excess norleucine media accumulate cyanogen bromide-resistant species of proteins after the supply is exhausted. Bacteria, transformed by recombinant plasmid pIPD37 carrying adk gene under limiting norleucine, synthesize 16-20% adenylate kinase molecules having all 6 residues replaced norleucine. Species showing only partial replacement are identified sodium dodecyl sulfate-polyacrylamide gel electrophoresis bromide treatment pure enzyme....
Voltage-dependent potassium (Kv) channels are tetramers of six transmembrane domain (S1–S6) proteins. Crystallographic data demonstrate that the tetrameric pore (S5–S6) is surrounded by four voltage sensor domains (S1–S4). One key question remains: how do sensors (S4) regulate gating? Previous mutagenesis obtained on Kv channel KCNQ1 highlighted critical role specific residues in both S4-S5 linker (S4S5L) and S6 C terminus (S6T). From these data, we hypothesized S4S5L behaves like a ligand...
The precise mechanism leading to profound immunodeficiency of HIV-infected patients is still only partially understood. Here, we show that more than 80% CD4+ T cells from have morphological abnormalities. Their membranes exhibited numerous large abnormal membrane microdomains (aMMDs), which trap and inactivate physiological receptors, such as for IL-7. In patient plasma, identified phospholipase A2 group IB (PLA2G1B) the key molecule responsible formation aMMDs. At concentrations, PLA2G1B...
The glycine-tyrosine-glycine (GYG) sequence in the p-loop of K+ channel subunits lines a narrow pore through which ions pass single file intercalated by water molecules. Mutation motif can give rise to non-selective channels, but it is clear that other structural features are also required for selectivity because, instance, recently identified class cyclic nucleotide-gated pacemaker channels has GYG poorly selective. We show mutation charged glutamate and arginine residues behind filter...
Serine proteases of the chymotrypsin family have maintained a common fold over an evolutionary span more than one billion years. Notwithstanding modest changes in sequence, this class enzymes has developed wide variety substrate specificities and important biological functions. Remarkably, C-terminal portion sequence protease domain accounts fully for functional diversity. This is often encoded by single exon contains most residues forming contact surface active site P1–P3 substrate, as well...
Three-dimensional models of thrombin complexed with large fragments the fibrinogen Aα and Bβ chains are presented. The consistent results recent mutagenesis studies information available on naturally occurring mutants. Thrombin recognizes an extended binding surface, key elements which Tyr76 in exosite I, located about 20 Å away from active site, aryl site close proximity to catalytic triad. A highly conserved aromatic-Pro-aromatic triplet motif is identified primed region other natural...