Mechanism of β-arrestin recruitment by the μ-opioid G protein-coupled receptor.

ABSTRACT: Agonists to the μ-opioid G protein-coupled receptor (μOR) can alleviate pain through activation of G protein signaling, but they can also induce β-arrestin activation, leading to such side effects as respiratory depression. Biased ligands to μOR that induce G protein signaling without inducing β-arrestin signaling can alleviate pain while reducing side effects. However, the mechanism for stimulating β-arrestin signaling is not known, making it difficult to design optimum biased ligands. We use extensive molecular dynamics simulations to determine three-dimensional (3D) structures of activated β-arrestin2 stabilized by phosphorylated μOR bound to the morphine and D-Ala², N-MePhe⁴, Gly-ol]-enkephalin (DAMGO) nonbiased agonists and to the TRV130 biased agonist. Fo

SUBMITTER: Mafi A 

PROVIDER: S-EPMC7368253 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature