Global insights into the fine tuning of human A_2AAR conformational dynamics in a ternary complex with an engineered G protein viewed by NMR.

ABSTRACT: G protein-coupled receptor (GPCR) conformational plasticity enables formation of ternary signaling complexes with intracellular proteins in response to binding extracellular ligands. We investigate the dynamic process of GPCR complex formation in solution with the human A_2A adenosine receptor (A_2AAR) and an engineered G_s protein, mini-G_s. 2D nuclear magnetic resonance (NMR) data with uniform stable isotope-labeled A_2AAR enabled a global comparison of A_2AAR conformations between complexes with an agonist and mini-G_s and with an agonist alone. The two conformations are similar and show subtle differences at the receptor intracellular surface, supporting a model whereby agonist binding alone is sufficient to populate

SUBMITTER: Ferre G 

PROVIDER: S-EPMC9832913 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature