Insight into partial agonism by observing multiple equilibria for ligand-bound and G_s-mimetic nanobody-bound β₁-adrenergic receptor.

ABSTRACT: A complex conformational energy landscape determines G-protein-coupled receptor (GPCR) signalling via intracellular binding partners (IBPs), e.g., G_s and β-arrestin. Using ¹³C methyl methionine NMR for the β₁-adrenergic receptor, we identify ligand efficacy-dependent equilibria between an inactive and pre-active state and, in complex with G_s-mimetic nanobody, between more and less active ternary complexes. Formation of a basal activity complex through ligand-free nanobody-receptor interaction reveals structural differences on the cytoplasmic receptor side compared to the full agonist-bound nanobody-coupled form, suggesting that ligand-induced variations in G-protein interaction underpin partial agonism. Significant differences in receptor dynamic

SUBMITTER: Solt AS 

PROVIDER: S-EPMC5702606 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature