Conformational plasticity of ligand-bound and ternary GPCR complexes studied by ¹⁹F NMR of the β₁-adrenergic receptor.

ABSTRACT: G-protein-coupled receptors (GPCRs) are allosteric signaling proteins that transmit an extracellular stimulus across the cell membrane. Using ¹⁹F NMR and site-specific labelling, we investigate the response of the cytoplasmic region of transmembrane helices 6 and 7 of the β₁-adrenergic receptor to agonist stimulation and coupling to a G_s-protein-mimetic nanobody. Agonist binding shows the receptor in equilibrium between two inactive states and a pre-active form, increasingly populated with higher ligand efficacy. Nanobody coupling leads to a fully active ternary receptor complex present in amounts correlating directly with agonist efficacy, consistent with partial agonism. While for different agonists the helix 6 environment in the active-state ternary comp

SUBMITTER: Frei JN 

PROVIDER: S-EPMC6997182 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature