GPCRome-wide analysis of G-protein-coupling diversity using a computational biology approach.

ABSTRACT: GPCRs are master regulators of cell signaling by transducing extracellular stimuli into the cell via selective coupling to intracellular G-proteins. Here we present a computational analysis of the structural determinants of G-protein-coupling repertoire of experimental and predicted 3D GPCR-G-protein complexes. Interface contact analysis recapitulates structural hallmarks associated with G-protein-coupling specificity, including TM5, TM6 and ICLs. We employ interface contacts as fingerprints to cluster G_s vs G_i complexes in an unsupervised fashion, suggesting that interface residues contribute to selective coupling. We experimentally confirm on a promiscuous receptor (CCKAR) that mutations of some of these specificity-determining positions bias the coupling selectivit

SUBMITTER: Matic M 

PROVIDER: S-EPMC10356834 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature