A5080348980- Receptor Mechanisms and Signaling
- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- Neuropeptides and Animal Physiology
- Mass Spectrometry Techniques and Applications
- Bacterial Genetics and Biotechnology
- Monoclonal and Polyclonal Antibodies Research
- Force Microscopy Techniques and Applications
- Biochemical Analysis and Sensing Techniques
- Regulation of Appetite and Obesity
- Pharmacological Effects and Assays
- NMR spectroscopy and applications
- Photosynthetic Processes and Mechanisms
- Advanced NMR Techniques and Applications
- Bacteriophages and microbial interactions
- Protein Kinase Regulation and GTPase Signaling
- RNA and protein synthesis mechanisms
- Metabolomics and Mass Spectrometry Studies
- Mechanical and Optical Resonators
- Adipose Tissue and Metabolism
- Fuel Cells and Related Materials
- Photoreceptor and optogenetics research
Stanford University
2022-2025
University of Milan
2024
Laboratoire de Biologie Physico-Chimique des Protéines Membranaires
2016-2023
Institut de Biologie Physico-Chimique
2014-2021
Université Paris Cité
2014-2021
Centre National de la Recherche Scientifique
2016-2021
Stanford Medicine
2021
Sorbonne Paris Cité
2016-2019
Sorbonne Université
2016-2019
Université Paris Sciences et Lettres
2017-2018
Mapping the conformational landscape of G protein-coupled receptors (GPCRs), and in particular how this is modulated by membrane environment, required to gain a clear picture signaling proceeds. To end, we have developed an original strategy based on solution-state nuclear magnetic resonance combined with efficient isotope labeling scheme. This was applied typical GPCR, leukotriene B4 receptor BLT2, reconstituted lipid bilayer. Because this, are able provide direct evidence that BLT2...
Significance Many proteins are located in lipid membranes surrounding cells and subcellular organelles. The membrane can impart important structural functional effects on the protein, making understanding of this interaction critical. Here, we apply computational simulation to identification conserved binding sites an highly bacterial Sec translocase (SecA-SecYEG), which uses ATP proton-motive force (PMF) secrete across plasma membrane. We experimentally validate these use analyses...
Summary G protein-coupled receptors (GPCRs) activate heterotrimeric proteins by stimulating the exchange of guanine nucleotide in Gα subunit. To visualize this mechanism, we developed a time-resolved cryo-EM approach that examines progression ensembles pre-steady-state intermediates GPCR-G protein complex. Using variability analysis to monitor transitions stimulatory Gs complex with β 2 -adrenergic receptor (β AR) at short sequential time points after GTP addition, identified conformational...
G protein-coupled receptors (GPCRs) exhibit varying degrees of selectivity for different protein isoforms. Despite the abundant structures GPCR-G complexes, little is known about mechanism coupling specificity. The β2-adrenergic receptor an example GPCR with high Gαs, stimulatory adenylyl cyclase, and much weaker Gαi family proteins inhibiting cyclase. By developing a Gαi-biased agonist (LM189), we provide structural biophysical evidence supporting that distinct conformations at ICL2 TM6 are...
G protein coupled receptors (GPCRs) exhibit varying degrees of selectivity for different isoforms. Despite the abundant structures GPCR-G complexes, little is known about mechanism coupling specificity. The β2-adrenergic receptor an example GPCR with high Gαs, stimulatory adenylyl cyclase, and much weaker Gαi family proteins inhibiting cyclase. By developing a new Gαi-biased agonist (LM189), we provide structural biophysical evidence supporting that distinct conformations at ICL2 TM6 are...
Abstract Cell membranes represent a complex and variable medium in time space of lipids proteins. Their physico-chemical properties are determined by lipid components which can turn influence the biological function membranes. Here, we used hydrostatic pressure to study close dynamic relationships between membrane Experiments on β –barrel OmpX α –helical BLT2 G Protein-Coupled Receptor nanodiscs different compositions reveal conformational landscapes intimately linked lipids. Pressure modify...
Abstract G Protein-Coupled receptors represent the main communicating pathway for signals from outside to inside of most eukaryotic cells. They define largest family integral membrane at surface cells and constitute target current drugs on market. The low affinity leukotriene receptor BLT2 is a involved in pro- anti-inflammatory pathways can be activated by various unsaturated fatty acid compounds. We present here NMR structure agonist 12–HHT its BLT2-bound state model interaction ligand...
There is increasing support for water molecules playing a role in signal propagation through G protein-coupled receptors (GPCRs). However, exploration of the hydration features GPCRs still its infancy. Here, we combined site-specific labeling with unnatural amino acids to molecular dynamics delineate how local ghrelin receptor growth hormone secretagogue (GHSR) rearranged upon activation. We found that GHSR characterized by specific pattern selectively remodeled pharmacologically distinct...
Abstract The transport of proteins across or into membranes is a vital biological process, achieved in every cell by the conserved Sec machinery. In bacteria, SecYEG combines with SecA motor protein for secretion pre-proteins plasma membrane, powered ATP hydrolysis and trans-membrane proton-motive-force (PMF). activities are modulated membrane lipids, particularly cardiolipin, specialised phospholipid known to associate range energy-transducing machines. Here, we identify two specific...