Biased activation of the vasopressin V2 receptor probed by molecular dynamics simulations, NMR and pharmacological studies.

ABSTRACT: G protein-coupled receptors (GPCRs) control critical cell signaling. Their response to extracellular stimuli involves conformational changes to convey signals to intracellular effectors, among which the most important are G proteins and β-arrestins (βArrs). Biased activation of one pathway is a field of intense research in GPCR pharmacology. Combining NMR, site-directed mutagenesis, molecular pharmacology, and molecular dynamics (MD) simulations, we studied the conformational diversity of the vasopressin V2 receptor (V2R) bound to different types of ligands: the antagonist Tolvaptan, the endogenous unbiased agonist arginine-vasopressin, and MCF14, a partial Gs protein-biased agonist. A double-labeling NMR scheme was developed to study the receptor conformational changes and ligand binding:

SUBMITTER: Fouillen A 

PROVIDER: S-EPMC11550766 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature