Cryo-EM structure of the human adenosine A2B receptor-Gs signaling complex

doi:10.1126/sciadv.add3709

	Cryo-EM structure of the human adenosine A2B receptor-Gs signaling complex
	Chen, Ying 1,2; Zhang, Jinyi3,4 ; Weng, Yuan 1,2; Xu, Yueming 1,2; Lu, Weiqiang 1,2; Liu, Wei 5,6; Liu, Mingyao 1,2; Hua, Tian3,4 ; Song, Gaojie 1,2
	2022-12-23
发表期刊	SCIENCE ADVANCES (IF:11.7[JCR-2023],13.7[5-Year])
ISSN	2375-2548
卷号	8 期号:51
发表状态	已发表
DOI	10.1126/sciadv.add3709
摘要	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 ag-onists NECA and BAY60-6583, each coupled to an engineered Gs protein. The structures reveal conserved orthos-teric 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. Commons NonCommercial License
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收录类别	SCI ; EI
语种	英语
资助项目	National Key Research and Development Program of China["2018YFA0507001","2018YFA0507000"] ; National Natural Science Foundation of China[32171215] ; basic research program of Science and Technology Commission of Shanghai Municipality[21JC1402400] ; National Science Fund for Distinguished Young Scholars[32022038]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000906626700008
出版者	AMER ASSOC ADVANCEMENT SCIENCE
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/274936
专题	生命科学与技术学院_博士生 iHuman研究所_PI研究组_华甜组
通讯作者	Hua, Tian; Song, Gaojie
作者单位	1.East China Normal Univ, Inst Biomed Sci, Shanghai Frontiers Sci Ctr Genome Editing & Cell T, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China 2.East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China 3.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 5.Med Coll Wisconsin, Canc Ctr, Milwaukee, WI 53226 USA 6.Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA
通讯作者单位	iHuman研究所; 生命科学与技术学院
推荐引用方式 GB/T 7714	Chen, Ying,Zhang, Jinyi,Weng, Yuan,et al. Cryo-EM structure of the human adenosine A2B receptor-Gs signaling complex[J]. SCIENCE ADVANCES,2022,8(51).
APA	Chen, Ying.,Zhang, Jinyi.,Weng, Yuan.,Xu, Yueming.,Lu, Weiqiang.,...&Song, Gaojie.(2022).Cryo-EM structure of the human adenosine A2B receptor-Gs signaling complex.SCIENCE ADVANCES,8(51).
MLA	Chen, Ying,et al."Cryo-EM structure of the human adenosine A2B receptor-Gs signaling complex".SCIENCE ADVANCES 8.51(2022).