7XY7

Adenosine receptor bound to a non-selective agonist in complex with a G protein obtained by cryo-EM

Summary for 7XY7

• Entry DOI: 10.2210/pdb7xy7/pdb
• EMDB information: 33513
• Descriptor: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (5 entities in total)
• Functional Keywords: g protein coupled-receptor, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 145668.64

Authors

Zhang, J.Y.,Chen, Y.,Hua, T.,Song, G.J. (deposition date: 2022-05-31, release date: 2023-05-03, Last modification date: 2024-10-23)

Primary citation

Chen, Y.,Zhang, J.,Weng, Y.,Xu, Y.,Lu, W.,Liu, W.,Liu, M.,Hua, T.,Song, G.
Cryo-EM structure of the human adenosine A 2B receptor-G s signaling complex.
Sci Adv, 8:eadd3709-eadd3709, 2022

PubMed Abstract: The human adenosine A receptor (AR) is a class A G protein-coupled receptor that is involved in several major physiological and pathological processes throughout the body. AR recognizes its ligands adenosine and NECA with relatively low affinity, but the detailed mechanism for its ligand recognition and signaling is still elusive. Here, we present two structures determined by cryo-electron microscopy of AR bound to its agonists NECA and BAY60-6583, each coupled to an engineered G protein. The structures reveal conserved orthosteric binding pockets with subtle differences, whereas the selectivity or specificity can mainly be attributed to regions extended from the orthosteric pocket. We also found that BAY60-6583 occupies a secondary pocket, where residues V250 and N273 were two key determinants for its selectivity against AR. This study offers a better understanding of ligand selectivity for the adenosine receptor family and provides a structural template for further development of AR ligands for related diseases.

PubMed: 36563137
DOI: 10.1126/sciadv.add3709

Experimental method

ELECTRON MICROSCOPY (3.26 Å)