Structural and Functional Analysis of a β₂-Adrenergic Receptor Complex with GRK5.

ABSTRACT: The phosphorylation of agonist-occupied G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) functions to turn off G-protein signaling and turn on arrestin-mediated signaling. While a structural understanding of GPCR/G-protein and GPCR/arrestin complexes has emerged in recent years, the molecular architecture of a GPCR/GRK complex remains poorly defined. We used a comprehensive integrated approach of cross-linking, hydrogen-deuterium exchange mass spectrometry (MS), electron microscopy, mutagenesis, molecular dynamics simulations, and computational docking to analyze GRK5 interaction with the β₂-adrenergic receptor (β₂AR). These studies revealed a dynamic mechanism of complex formation that involves large conformational changes in the GRK5 RH/catalytic domain in

SUBMITTER: Komolov KE 

PROVIDER: S-EPMC5526774 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature