Molecular determinants of ligand efficacy and potency in GPCR signaling.

ABSTRACT: Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) bind to extracellular ligands and drugs and modulate intracellular responses through conformational changes. Despite their importance as drug targets, the molecular origins of pharmacological properties such as efficacy (maximum signaling response) and potency (the ligand concentration at half-maximal response) remain poorly understood for any ligand-receptor-signaling system. We used the prototypical adrenaline-β2 adrenergic receptor-G protein system to reveal how specific receptor residues decode and translate the information encoded in a ligand to mediate a signaling response. We present a data science framework to integrate pharmacological and structural data to uncover structural changes and allost

SUBMITTER: Heydenreich FM 

PROVIDER: S-EPMC7615523 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature