Structural Insight into G Protein-Coupled Receptor Signaling Efficacy and Bias between Gs and β-Arrestin.

ABSTRACT: G protein-coupled receptors (GPCRs) form the largest family of membrane proteins involved in signal transduction. Because of their ability to regulate a wide range of cellular responses and their dysregulation being associated with many diseases, GPCRs remain a key therapeutic target for several clinical indications. In recent years, it has been demonstrated that ligands for a given receptor can engage distinct pathways with different relative efficacies, a concept known as biased signaling or functional selectivity. However, the structural determinants of this phenomenon remain poorly understood. Using the β2-adrenergic receptor as a model, we identified a linker residue (L124^3.43) between the known PIF and NPxxY structural motifs, that plays a central role in the differential

SUBMITTER: Picard LP 

PROVIDER: S-EPMC7088954 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature