腺苷受体
腺苷
受体
G蛋白偶联受体
化学
配体(生物化学)
腺苷A2B受体
细胞生物学
立体化学
生物物理学
生物化学
生物
兴奋剂
作者
Ying Chen,Jinyi Zhang,Yuan Weng,Yueming Xu,Weiqiang Lü,Wei Liu,Mingyao Liu,Tian Hua,Gaojie Song
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2022-12-23
卷期号:8 (51)
被引量:12
标识
DOI:10.1126/sciadv.add3709
摘要
The human adenosine A 2B receptor (A 2B R) is a class A G protein–coupled receptor that is involved in several major physiological and pathological processes throughout the body. A 2B R 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 A 2B R bound to its agonists NECA and BAY60-6583, each coupled to an engineered G s 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 6.51 and N273 7.36 were two key determinants for its selectivity against A 2B R. This study offers a better understanding of ligand selectivity for the adenosine receptor family and provides a structural template for further development of A 2B R ligands for related diseases.
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