A5052118441- Receptor Mechanisms and Signaling
- Photoreceptor and optogenetics research
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- Retinal Development and Disorders
- Neuroscience and Neuropharmacology Research
- Protein Kinase Regulation and GTPase Signaling
- Mass Spectrometry Techniques and Applications
- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- Circadian rhythm and melatonin
- Chemokine receptors and signaling
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
- Photochromic and Fluorescence Chemistry
- Neurobiology and Insect Physiology Research
- Peptidase Inhibition and Analysis
- Computational Drug Discovery Methods
- Spectroscopy and Quantum Chemical Studies
- Photosynthetic Processes and Mechanisms
- HER2/EGFR in Cancer Research
- Machine Learning in Bioinformatics
- Cell Adhesion Molecules Research
- Molecular spectroscopy and chirality
- RNA and protein synthesis mechanisms
Paul Scherrer Institute
2016-2025
SIB Swiss Institute of Bioinformatics
2022-2025
Molecular Research Institute
2014-2025
Computational Physics (United States)
2025
Center for Life Sciences
2025
Universitat Autònoma de Barcelona
2002-2015
University of Amsterdam
2015
Heptares Therapeutics (United Kingdom)
2015
Stanford University
2005-2007
Universidad Complutense de Madrid
2002
G protein-coupled receptors (GPCR) are seven transmembrane helix proteins that couple binding of extracellular ligands to conformational changes and activation intracellular proteins, GPCR kinases, arrestins. Constitutively active mutants ubiquitously found among GPCRs increase the inherent basal activity receptor, which often correlates with a pathological outcome. Here, we have used M257Y 6.40 constitutively mutant photoreceptor rhodopsin in combination specific C-terminal fragment from...
Abstract Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs) 1 . A photon absorbed 11- cis retinal chromophore rhodopsin, which isomerizes within 200 femtoseconds to all- trans conformation 2 , thereby initiating cellular signal transduction processes that ultimately lead vision. However, intramolecular mechanism photoactivated induces activation events inside remains experimentally unclear. Here we use ultrafast time-resolved crystallography at...
The beta(2) adrenergic receptor (beta(2)AR) is a prototypical family A G protein-coupled (GPCR) and an excellent model system for studying the mechanism of GPCR activation. beta(2)AR agonist binding site well characterized, there wealth structurally related ligands with functionally diverse properties. In present study, we use catechol (1,2-benzenediol, structural component catecholamine agonists) as molecular probe to identify mechanistic differences between activation by agonists, such...
G protein-coupled receptors (GPCRs) mediate the majority of physiologic responses to hormones and neurotransmitters. However, many GPCRs exhibit varying degrees agonist-independent protein activation. This phenomenon is referred as basal or constitutive activity. For these GPCRs, drugs classified inverse agonists can suppress There a growing body evidence that activity physiologically relevant, ability drug inhibit may influence its therapeutic properties. molecular mechanism for activation...
G protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters, representing the largest group of therapeutic targets. Recent studies show some GPCRs signal through both protein arrestin pathways in a ligand-specific manner. Ligands direct signaling specific pathway known as biased ligands. The arginine-vasopressin type 2 receptor (V2R), prototypical peptide-activated GPCR, is an ideal model system investigate...
Cellular functions of arrestins are determined in part by the pattern phosphorylation on G protein-coupled receptors (GPCRs) to which bind. Despite high-resolution structural data bound phosphorylated receptor C-termini, functional role each site remains obscure. Here, we employ a library synthetic phosphopeptide analogues GPCR rhodopsin C-terminus and determine ability these peptides bind activate using variety biochemical biophysical methods. We further characterize how modulate...
The structure of CCR5 in complex with [6P4]CCL5 and the G i protein reveals its activation mechanism.
β-arrestins mediate regulatory processes for over 800 different G protein-coupled receptors (GPCRs) by adopting specific conformations that result from the geometry of GPCR-β-arrestin complex. However, whether β-arrestin1 and 2 respond differently binding to same GPCR is still unknown. Employing GRK knockout cells lacking finger-loop-region, we show two isoforms prefer associate with active parathyroid hormone 1 receptor (PTH1R) in complex configurations ("hanging" "core"). Furthermore,...
Animal opsins are G protein coupled receptors that have evolved to sense light by covalently binding a retinal chromophore via protonated (positively charged) Schiff base. A negatively charged amino acid in the opsin, acting as counterion, stabilises proton on base, which is essential for sensitivity visible light. In this study, we investigate spectroscopic properties of unique class from reef-building coral belonging anthozoan-specific opsin II group (ASO-II opsins), intriguingly lack...
The important and diverse biological functions of β-adrenergic receptors (βARs) have promoted the search for compounds to stimulate or inhibit their activity. In this regard, unraveling molecular basis ligand binding/unbinding events is essential understand pharmacological properties these G protein-coupled receptors. study, we use steered dynamics simulation method describe, in atomic detail, unbinding process two inverse agonists, which been recently co-crystallized with β1 β2ARs subtypes,...