Unraveling allostery within the angiotensin II type 1 receptor for Gα_q and β-arrestin coupling.

ABSTRACT: G protein-coupled receptors engage both G proteins and β-arrestins, and their coupling can be biased by ligands and mutations. Here, to resolve structural elements and mechanisms underlying effector coupling to the angiotensin II (AngII) type 1 receptor (AT1R), we combined alanine scanning mutagenesis of the entire sequence of the receptor with pharmacological profiling of Gα_q and β-arrestin engagement to mutant receptors and molecular dynamics simulations. We showed that Gα_q coupling to AT1R involved a large number of residues spread across the receptor, whereas fewer structural regions of the receptor contributed to β-arrestin coupling regulation. Residue stretches in transmembrane domain 4 conferred β-arrestin bias and represented an important structural element in

SUBMITTER: Cao Y 

PROVIDER: S-EPMC10640921 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature