Sub-millisecond conformational dynamics of the A_2A adenosine receptor revealed by single-molecule FRET.

ABSTRACT: The complex pharmacology of G-protein-coupled receptors (GPCRs) is defined by their multi-state conformational dynamics. Single-molecule Förster Resonance Energy Transfer (smFRET) is well suited to quantify dynamics for individual protein molecules; however, its application to GPCRs is challenging. Therefore, smFRET has been limited to studies of inter-receptor interactions in cellular membranes and receptors in detergent environments. Here, we performed smFRET experiments on functionally active human A_2A adenosine receptor (A_2AAR) molecules embedded in freely diffusing lipid nanodiscs to study their intramolecular conformational dynamics. We propose a dynamic model of A_2AAR activation that involves a slow (>2 ms) exchange between the active-like and inacti

SUBMITTER: Maslov I 

PROVIDER: S-EPMC10070357 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature