Molecular Mechanism for Ligand Recognition and Subtype Selectivity of alpha(2C) Adrenergic Receptor
Chen, Xiaoyu1,2,3,4; Xu, Yueming1; Qu, Lu1,4,5; Wu, Lijie1; Han, Gye Won6,7; 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, Shuguang8,9,10; Wang, Ling1; Hu, Tao1,2,3,4; Tao, Houchao1; Sun, Yaping11; Song, Yunpeng11; Hu, Liaoyuan11; Liu, Zhi-Jie1,2; Stevens, Raymond C.1,2; Zhao, Suwen1,2; Wu, Dong1; Zhong, Guisheng1,2
2019-12-03
Source PublicationCELL REPORTS
ISSN2211-1247
Volume29Issue:10Pages:2936-+
Status已发表
DOI10.1016/j.celrep.2019.10.112
AbstractAdrenergic 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.
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Indexed BySCI
Language英语
Funding ProjectNatural Science Foundation of Shanghai grant[16ZR1448500]
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000500822900002
PublisherCELL PRESS
WOS KeywordCOLD-INDUCED VASOCONSTRICTION ; CATECHOLAMINE RELEASE ; CRYSTAL-STRUCTURES ; AGONIST BINDING ; ALPHA(2C)-ADRENOCEPTORS ; MEMBRANE ; COMPLEX ; DOMAIN
Original Document TypeArticle
Citation statistics
Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://kms.shanghaitech.edu.cn/handle/2MSLDSTB/104521
CollectioniHuman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
Corresponding AuthorZhao, Suwen; Wu, Dong; Zhong, Guisheng
Affiliation1.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
First Author AffilicationiHuman Institute;  School of Life Science and Technology
Corresponding Author AffilicationiHuman Institute;  School of Life Science and Technology
First Signature AffilicationiHuman Institute
Recommended Citation
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-+.
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