β2-adrenoceptor ligand efficacy is tuned by a two-stage interaction with the Gαs C terminus.

ABSTRACT: Classical pharmacological models have incorporated an "intrinsic efficacy" parameter to capture system-independent effects of G protein-coupled receptor (GPCR) ligands. However, the nonlinear serial amplification of downstream signaling limits quantitation of ligand intrinsic efficacy. A recent biophysical study has characterized a ligand "molecular efficacy" that quantifies the influence of ligand-dependent receptor conformation on G protein activation. Nonetheless, the structural translation of ligand molecular efficacy into G protein activation remains unclear and forms the focus of this study. We first establish a robust, accessible, and sensitive assay to probe GPCR interaction with G protein and the Gα C terminus (G-peptide), an established structural determinant of G protein selecti

SUBMITTER: Kim K 

PROVIDER: S-EPMC7980469 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature