EMD-33513

Single-particle
3.26 Å
EMD-33513 Deposition: 31/05/2022
Map released: 03/05/2023
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-33513

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

EMD-33513

Single-particle
3.26 Å
EMD-33513 Deposition: 31/05/2022
Map released: 03/05/2023
Last modified: 23/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Oplophorus gracilirostris
Sample: Adenosine receptor A2B bound to a non-selective agonist in complex with G protein obtained by cryo-EM
Fitted models: 7xy7 (Avg. Q-score: 0.443)

Deposition Authors: Zhang JY, Chen Y , Hua T , Song GJ
Cryo-EM structure of the human adenosine A 2B receptor-G s signaling complex.
Chen Y , Zhang J , Weng Y , Xu Y , Lu W , Liu W, Liu M , Hua T , Song G
(2022) Sci Adv , 8 , eadd3709 - eadd3709
PUBMED: 36563137
DOI: doi:10.1126/sciadv.add3709
ISSN: 2375-2548
Abstract:
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.