Molecular Mechanism for Ligand Recognition and Subtype Selectivity of alpha(2C) Adrenergic Receptor

doi:10.1016/j.celrep.2019.10.112

	Molecular Mechanism for Ligand Recognition and Subtype Selectivity of alpha(2C) Adrenergic Receptor
	Chen, Xiaoyu1,2,3,4 ; Xu, Yueming1 ; Qu, Lu 1,4,5; Wu, Lijie1 ; Han, Gye Won 6,7; Guo, Yu1,2,4 ; Wu, Yiran1 ; Zhou, Qingtong1 ; Sun, Qianqian1 ; Chu, Cenfeng1,2,4 ; Yang, Jie1,2,4 ; Yang, Liu1,2,4 ; Wang, Quan1,2,4 ; Yuan, Shuguang 8,9,10; Wang, Ling1 ; Hu, Tao1,2,3,4 ; Tao, Houchao1 ; Sun, Yaping 11; Song, Yunpeng 11; Hu, Liaoyuan 11; Liu, Zhi-Jie1,2 ; Stevens, Raymond C.1,2 ; Zhao, Suwen1,2 ; Wu, Dong1 ; Zhong, Guisheng1,2
	2019-12-03
发表期刊	CELL REPORTS
ISSN	2211-1247
卷号	29 期号:10 页码:2936-+
发表状态	已发表
DOI	10.1016/j.celrep.2019.10.112
摘要	Adrenergic G-protein-coupled receptors (GPCRs) mediate different cellular signaling pathways in the presence of endogenous catecholamines and play important roles in both physiological and pathological conditions. Extensive studies have been carried out to investigate the structure and function of beta adrenergic receptors (beta ARs). However, the structure of alpha adrenergic receptors (alpha ARs) remains to be determined. Here, we report the structure of the human alpha(2C) adrenergic receptor (alpha(2C)AR) with the non-selective antagonist, RS79948, at 2.8 angstrom. Our structure, mutations, modeling, and functional experiments indicate that a alpha(2C)AR-specific D206(ECL2)-R409(ECL3)-Y405(6.58) network plays a role in determining alpha(2) adrenergic subtype selectivity. Furthermore, our results show that a specific loosened helix at the top of TM4 in alpha(2C)AR is involved in receptor activation. Together, our structure of human alpha(2C)AR-RS79948 provides key insight into the mechanism underlying the alpha(2) adrenergic receptor activation and subtype selectivity.
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	Natural Science Foundation of Shanghai grant[16ZR1448500]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000500822900002
出版者	CELL PRESS
WOS关键词	COLD-INDUCED VASOCONSTRICTION ; CATECHOLAMINE RELEASE ; CRYSTAL-STRUCTURES ; AGONIST BINDING ; ALPHA(2C)-ADRENOCEPTORS ; MEMBRANE ; COMPLEX ; DOMAIN
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/104521
专题	iHuman研究所_公共科研平台_IT平台 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_生命科学电镜平台 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_硕士生生命科学与技术学院_博士生
通讯作者	Zhao, Suwen; Wu, Dong; Zhong, Guisheng
作者单位	1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 6.Univ Southern Calif, Bridge Inst, Dept Biol Sci, Los Angeles, CA 90089 USA 7.Univ Southern Calif, Bridge Inst, Dept Chem, Los Angeles, CA 90089 USA 8.Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen 518055, Guangdong, Peoples R China 9.Univ Warsaw, Fac Chem, Lab Biomodelling, PL-02093 Warsaw, Poland 10.Univ Warsaw, Biol & Chem Res Ctr, PL-02093 Warsaw, Poland 11.Amgen Biopharmaceut R&D Shanghai, Amgen Asia R&D Ctr, Shanghai 201210, Peoples R China
第一作者单位	iHuman研究所; 生命科学与技术学院
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	Chen, Xiaoyu,Xu, Yueming,Qu, Lu,et al. Molecular Mechanism for Ligand Recognition and Subtype Selectivity of alpha(2C) Adrenergic Receptor[J]. CELL REPORTS,2019,29(10):2936-+.
APA	Chen, Xiaoyu.,Xu, Yueming.,Qu, Lu.,Wu, Lijie.,Han, Gye Won.,...&Zhong, Guisheng.(2019).Molecular Mechanism for Ligand Recognition and Subtype Selectivity of alpha(2C) Adrenergic Receptor.CELL REPORTS,29(10),2936-+.
MLA	Chen, Xiaoyu,et al."Molecular Mechanism for Ligand Recognition and Subtype Selectivity of alpha(2C) Adrenergic Receptor".CELL REPORTS 29.10(2019):2936-+.