A5088660733- Lipid Membrane Structure and Behavior
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- Proteoglycans and glycosaminoglycans research
- Bacterial Infections and Vaccines
- Animal Virus Infections Studies
- Animal Disease Management and Epidemiology
- Antimicrobial Peptides and Activities
- Hepatitis C virus research
- Sepsis Diagnosis and Treatment
- Machine Learning in Bioinformatics
- Viral Infections and Immunology Research
- RNA Interference and Gene Delivery
- Carbohydrate Chemistry and Synthesis
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Nanopore and Nanochannel Transport Studies
- Chemical Synthesis and Analysis
- Escherichia coli research studies
- Pneumonia and Respiratory Infections
- Enzyme Structure and Function
- Force Microscopy Techniques and Applications
BIOASTER
2017-2025
Université Grenoble Alpes
2012-2017
CEA Grenoble
2014-2017
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2014-2017
Laboratoire de Chimie et Biologie des Métaux
2012-2017
Institut de Biosciences et Biotechnologies
2017
Institut Pasteur
2015
Centre National de la Recherche Scientifique
2006-2014
University of Calgary
2008-2014
Centre de Recherches sur les Macromolécules Végétales
2010-2013
Cellular membranes separate distinct aqueous compartments, but can be breached by transient hydrophilic pores. A large energetic cost prevents pore formation, which is largely dependent on the composition and structure of lipid bilayer. The softness bilayers disordered pores make their characterization difficult. We use molecular-dynamics simulations with atomistic detail to study thermodynamics, kinetics, mechanism formation closure in DLPC, DMPC, DPPC bilayers, free energies 17, 45, 78...
The small membrane protein p7 of hepatitis C virus forms oligomers and exhibits ion channel activity essential for infectivity. These viroporin features render an attractive target antiviral drug development. In this study, from strain HCV-J (genotype 1b) was chemically synthesized purified measurements structure analyses. cation-selective channels in planar lipid bilayers at the single-channel level by patch clamp technique. Ion shown to be inhibited hexamethylene amiloride but not...
Membrane proteins are estimated to represent about 25% of open reading frames in fully sequenced genomes. However, the experimental study remains difficult. Considerable efforts have thus been made develop prediction methods. Most these were conceived detect transmembrane helices polytopic proteins. Alternatively, a membrane protein can be monotopic and anchored via an amphipathic helix inserted parallel way interface, so-called in-plane (IPM) anchors. This type anchor is still poorly...
We have investigated the thermodynamics of phospholipid flip-flop and desorption. Using a series PC (phosphatidylcholine) lipids with different lengths acyl tails, number unsaturated we calculated potentials mean force (PMFs) in atomistic molecular dynamics simulations. The PMFs describe free energy for moving single lipid molecule from water to center respective bilayer. move equilibrium bilayer is assumed be barrier flip-flop. find that strongly dependent on structure bilayer; ranging 16...
Abstract Computer simulations offer a valuable way to study membrane systems, from simple lipid bilayers large transmembrane protein complexes and lipid‐nucleic acid for drug delivery. Their accuracy depends on the quality of force field parameters used describe components particular system. We have implemented widely CHARMM22 CHARMM27 fields in GROMACS simulation package (i) combine with two sets united‐atom lipids parameters; (ii) allow comparisons other or lipid‐protein combinations. Our...
Heparan sulfate (HS), a polysaccharide of the glycosaminoglycan family characterized by unique level complexity, has emerged as key regulator many fundamental biological processes. Although it become clear that this class molecules exert their functions interacting with proteins, exact modes interaction still remain largely unknown. Here we report engineering 13C-labeled HS-like oligosaccharide defined oligosaccharidic sequence was used to investigate structural determinants involved in...
Heparan sulfate is a polysaccharide belonging to the glycaminoglycan family. It interacts with numerous proteins of extracellular matrix, in particular cellular growth factors. The number experimental protein–heparin complexes obtained by crystallography or nuclear magnetic resonance limited. Alternatively, computational approaches can be employed. Generally, they restrain conformation glycosidic rings and linkages order reduce complexity problem. Modeling interaction between protein heparan...
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a monotopic membrane anchored to the by an N-terminal in-plane amphipathic α-helix. This anchor essential for assembly of functional viral replication complex. Although amino acid sequences differ considerably, putative anchors with features were predicted in NS5A from related Flaviviridae family members, particular bovine diarrhea (BVDV), prototype representative genus Pestivirus. We report here NMR structure 1−28 BVDV presence...
Heparin/heparan sulfate interact with growth factors, chemokines, extracellular proteins, and receptors. Integrins are αβ heterodimers that serve as receptors for regulate cell behavior, participate in matrix assembly. Heparin binds to RGD‐dependent integrins (αIIbβ3, α5β1, αvβ3, αvβ5) RGD‐independent (α4β1, αXβ2, αMβ2), but their binding sites have not been located on integrins. We report the mapping of heparin ectodomain αvβ3 integrin by molecular modeling. The surface was scanned small...
The transport of lipids between membrane leaflets, also known as flip-flop, is a key process in regulating the lipid composition biological membranes. It important for growth biogenic membranes that are site synthesis. has been shown mere presence transmembrane alpha-helical peptides or proteins enhances rate flip-flop [Kol et al. (2001) Biochemistry 40, 10500-10506]. Using computational models natural phospholipids with different headgroups, we calculated free energy profiles transferring...
Nonstructural protein 5A (NS5A) is a membrane-associated essential component of the hepatitis C virus (HCV) replication complex. An N-terminal amphipathic alpha helix mediates in-plane membrane association HCV NS5A and at same time likely involved in specific protein-protein interactions required for assembly functional The aim this study was to identify determinants from related GB viruses pestiviruses. Although primary amino acid sequences differed considerably, putative anchor domains...
The adenylate cyclase toxin CyaA is involved in the early stages of infection by Bordetella pertussis, causative agent whooping cough. intoxicates target cells a direct translocation its catalytic domain (AC) across plasma membrane and produces supraphysiological levels cAMP, leading to cell death. molecular process AC remains largely unknown, however. We have previously shown that deletion residues 375–485 selectively abrogates into eukaryotic cells. further identified within this...
Cardiac ATP-sensitive potassium (K(ATP)) channels are key sensors and effectors of the metabolic status cardiomyocytes. Alteration in their expression impacts effectiveness maintaining cellular energy homeostasis resistance to injury. We sought determine how activation calcium/calmodulin-dependent protein kinase II (CaMKII), a central regulator calcium signaling, translates into reduced membrane current capacity cardiac K(ATP) channels. used real-time monitoring channel density,...
Abstract Heparan sulfate is abundantly present in the extracellular matrix. As other glycosaminoglycans, it synthesized Golgi apparatus and then exposed on cell surface. The glucuronidase activity of human heparanase plays a major role structural remodeling matrix, which underlies migration, hence tumor invasion. Heparanase therefore target for anti‐cancer treatment. Several inhibitors its enzymatic have been synthesized. However, their design limited by absence experimental structure...
Abstract Ligand-gated ion channels enable intercellular transmission of action potential through synapses by transducing biochemical messengers into electrical signal. We designed artificial ligand-gated coupling G protein-coupled receptors to the Kir6.2 potassium channel. These called channel-coupled offer complementary properties natural extending repertoire ligands those recognized fused receptors, generating more sustained signals and conferring selectivity. The first based on muscarinic...
Ion channel-coupled receptors (ICCR) are artificial proteins built from a G protein-coupled receptor and an ion channel. Their use as molecular biosensors is promising in diagnosis high-throughput drug screening. The concept of ICCR was initially validated with the combination muscarinic M2 inwardly rectifying potassium channel Kir6.2. A long protein engineering phase has led to biochemical characterization M2-Kir6.2 construct. However, its mechanism remains be elucidated. In particular, it...