Cryo-EM structure of the human adenosine A2B receptor-Gs signaling complex. Sci Adv 2022 Dec 23;8(51):eadd3709
Date
12/24/2022Pubmed ID
36563137Pubmed Central ID
PMC9788782DOI
10.1126/sciadv.add3709Scopus ID
2-s2.0-85144637416 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
The human adenosine A2B receptor (A2BR) is a class A G protein-coupled receptor that is involved in several major physiological and pathological processes throughout the body. A2BR 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 A2BR bound to its agonists NECA and BAY60-6583, each coupled to an engineered Gs 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 V2506.51 and N2737.36 were two key determinants for its selectivity against A2BR. This study offers a better understanding of ligand selectivity for the adenosine receptor family and provides a structural template for further development of A2BR ligands for related diseases.
Author List
Chen Y, Zhang J, Weng Y, Xu Y, Lu W, Liu W, Liu M, Hua T, Song GAuthor
Wei Liu PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdenosineAdenosine-5'-(N-ethylcarboxamide)
Cryoelectron Microscopy
GTP-Binding Proteins
Humans
Ligands
Receptor, Adenosine A2B
