Structural Basis of the Diversity of Adrenergic Receptors

doi:10.1016/j.celrep.2019.10.088

	Structural Basis of the Diversity of Adrenergic Receptors
	Qu, Lu 1,2,3; Zhou, Qingtong1 ; Xu, Yueming1 ; Guo, Yu1,4 ; Chen, Xiaoyu1,4 ; Yao, Deqiang1 ; Han, Gye Won 5,6; Liu, Zhi-Jie1,4 ; Stevens, Raymond C.1,5,6 ; Zhong, Guisheng1,4 ; Wu, Dong1 ; Zhao, Suwen1,4
	2019-12-03
发表期刊	CELL REPORTS
ISSN	2211-1247
卷号	29 期号:10 页码:2929-+
发表状态	已发表
DOI	10.1016/j.celrep.2019.10.088
摘要	Adrenergic receptors are highly homologous while at the same time display a wide diversity of ligand and G-protein binding, and understanding this diversity is key for designing selective or biased drugs for them. Here, we determine two crystal structures of the alpha(2A) adrenergic receptor (alpha(2A)AR) in complex with a partial agonist and an antagonist. Key non-conserved residues from the ligand-binding pocket (Phe(7.39) and Tyr(6.55)) to G-protein coupling region (Ile(34.51) and Lys(34.56)) are discovered to play a key role in the interplay between partial agonism and biased signaling of alpha(2A)AR, which provides insights into the diversity of ligand binding and G-protein coupling preference of adrenergic receptors and lays the foundation for the discovery of next-generation drugs targeting these receptors.
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	National Key R&D Program of China[2016YFC0905900] ; National Key R&D Program of China[2018YFA0507000] ; National Key R&D Program of China[2017YFC1001300]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000500822900001
出版者	CELL PRESS
WOS关键词	CRYSTAL-STRUCTURE ; DOCKING ; AGONIST ; BINDING ; PROTEINS ; GLIDE ; MICE
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/104520
专题	生命科学与技术学院_硕士生 iHuman研究所 iHuman研究所_特聘教授组_Andrej Sali组 iHuman研究所_特聘教授组_Raymond Stevens组 iHuman研究所_公共科研平台_IT平台 iHuman研究所_PI研究组_刘志杰组 iHuman研究所_PI研究组_陶厚朝组 iHuman研究所_PI研究组_赵素文组 iHuman研究所_PI研究组_钟桂生组 iHuman研究所_科学装置(X)_膜蛋白同步辐射线站生命科学与技术学院_博士生
通讯作者	Zhong, Guisheng; Wu, Dong; Zhao, Suwen
作者单位	1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 2.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 5.Univ Southern Calif, Dept Biol Sci, Bridge Inst, Los Angeles, CA 90089 USA 6.Univ Southern Calif, Dept Chem, Bridge Inst, Los Angeles, CA 90089 USA
第一作者单位	iHuman研究所
通讯作者单位	iHuman研究所; 生命科学与技术学院
第一作者的第一单位	iHuman研究所
推荐引用方式 GB/T 7714	Qu, Lu,Zhou, Qingtong,Xu, Yueming,et al. Structural Basis of the Diversity of Adrenergic Receptors[J]. CELL REPORTS,2019,29(10):2929-+.
APA	Qu, Lu.,Zhou, Qingtong.,Xu, Yueming.,Guo, Yu.,Chen, Xiaoyu.,...&Zhao, Suwen.(2019).Structural Basis of the Diversity of Adrenergic Receptors.CELL REPORTS,29(10),2929-+.
MLA	Qu, Lu,et al."Structural Basis of the Diversity of Adrenergic Receptors".CELL REPORTS 29.10(2019):2929-+.