Evolutionary association of receptor-wide amino acids with G protein-coupling selectivity in aminergic GPCRs.

ABSTRACT: G protein-coupled receptors (GPCRs) induce signal transduction pathways through coupling to four main subtypes of G proteins (G_s, G_i, G_q, and G_12/13), selectively. However, G protein selective activation mechanisms and residual determinants in GPCRs have remained obscure. Herein, we performed extensive phylogenetic analysis and identified specifically conserved residues for the aminergic receptors having similar coupling profiles. By integrating our methodology of differential evolutionary conservation of G protein-specific amino acids with structural analyses, we identified specific activation networks for G_s, G_i1, G_o, and G_q To validate that these networks could determine coupling selectivity we furth

SUBMITTER: Selcuk B 

PROVIDER: S-EPMC9133432 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature