Delineating the conformational landscape of the adenosine A_2A receptor during G protein coupling.

ABSTRACT: G-protein-coupled receptors (GPCRs) represent a ubiquitous membrane protein family and are important drug targets. Their diverse signaling pathways are driven by complex pharmacology arising from a conformational ensemble rarely captured by structural methods. Here, fluorine nuclear magnetic resonance spectroscopy (¹⁹F NMR) is used to delineate key functional states of the adenosine A_2A receptor (A_2AR) complexed with heterotrimeric G protein (Gα_sβ₁γ₂) in a phospholipid membrane milieu. Analysis of A_2AR spectra as a function of ligand, G protein, and nucleotide identifies an ensemble represented by inactive states, a G-protein-bound activation intermediate, and distinct nucleotide-free states associated with either

SUBMITTER: Huang SK 

PROVIDER: S-EPMC10266235 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature