Biased Signaling of the G-Protein-Coupled Receptor β₂AR Is Governed by Conformational Exchange Kinetics.

ABSTRACT: G-protein-coupled receptors (GPCRs) mediate a wide range of human physiological functions by transducing extracellular ligand binding events into intracellular responses. GPCRs can activate parallel, independent signaling pathways mediated by G proteins or β-arrestins. Whereas "balanced" agonists activate both pathways equally, "biased" agonists dominantly activate one pathway, which is of interest for designing GPCR-targeting drugs because it may mitigate undesirable side effects. Previous studies demonstrated that β-arrestin activation is associated with transmembrane helix VII (TM VII) of GPCRs. Here, single-molecule fluorescence spectroscopy with the β₂-adrenergic receptor (β₂AR) in the ligand-free state showed that TM VII spontaneously fluctuates between one inac

SUBMITTER: Lamichhane R 

PROVIDER: S-EPMC7213800 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature