Angiotensin Analogs with Divergent Bias Stabilize Distinct Receptor Conformations.

ABSTRACT: "Biased" G protein-coupled receptor (GPCR) agonists preferentially activate pathways mediated by G proteins or β-arrestins. Here, we use double electron-electron resonance spectroscopy to probe the changes that ligands induce in the conformational distribution of the angiotensin II type I receptor. Monitoring distances between 10 pairs of nitroxide labels distributed across the intracellular regions enabled mapping of four underlying sets of conformations. Ligands from different functional classes have distinct, characteristic effects on the conformational heterogeneity of the receptor. Compared to angiotensin II, the endogenous agonist, agonists with enhanced Gq coupling more strongly stabilize an "open" conformation with an accessible transducer-binding site. β-arrestin-biased agonists d

SUBMITTER: Wingler LM 

PROVIDER: S-EPMC6475118 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature