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GPCRs steer G(i) and G(s) selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors

文献类型：期刊论文

作者Huang, Sijie10,11,12; Xu, Peiyu11,12; Shen, Dan-Dan1,7,8,9; Simon, Icaro A.2,5,6; Mao, Chunyou1,7,8,9; Tan, Yangxia10,11,12; Zhang, Huibing1,7,8,9; Harpsoe, Kasper6; Li, Huadong10,11,12; Zhang, Yumu10,11,12
刊名MOLECULAR CELL
出版日期2022-07-21
卷号82期号:14页码:2681-+
ISSN号1097-2765
DOI10.1016/j.molcel.2022.05.031
通讯作者Zhang, Yan(zhang_yan@zju.edu.cn) ; Gloriam, David E.(david.gloriam@sund.ku.dk) ; Xu, H. Eric(eric.xu@simm.ac.cn)
英文摘要Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates 12 different G protein-coupled receptors (GPCRs) through selective coupling of G(s), G(i), or G(q) proteins. The structural basis for G protein subtype selectivity by these GPCRs remains elusive. Here, we report the structures of the serotonin receptors 5-HT4, 5-HT6, and 5-HT7 with G(s), and 5-HT4 with G(i1). The structures reveal that transmembrane helices TM5 and TM6 alternate lengths as a macro-switch to determine receptor's selectivity for G(s) and G(i), respectively. We find that the macro-switch by the TM5-TM6 length is shared by class A GPCR-G protein structures. Furthermore, we discover specific residues within TM5 and TM6 that function as micro-switches to form specific interactions with G(s) or G(i). Together, these results present a common mechanism of G(s) versus G(i) protein coupling selectivity or promiscuity by class A GPCRs and extend the basis of ligand recognition at serotonin receptors.
WOS关键词CRYO-EM STRUCTURE ; GS-PROTEIN ; ACTIVATION ; PREDICTION ; MECHANISM ; VALIDATION ; GENERATION ; PEPTIDE ; AGONIST ; BINDING
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
WOS记录号WOS:000841749300003
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/302278]  
专题中国科学院上海药物研究所
通讯作者Zhang, Yan; Gloriam, David E.; Xu, H. Eric
作者单位1.Zhejiang Univ, Liangzhu Lab, Med Ctr, Hangzhou 311121, Peoples R China
2.Vrije Univ Amsterdam, Div Med Chem, Amsterdam Inst Mol & Life Sci AIMMS, Fac Sci, De Boelelaan 1108, NL-1081 HZ Amsterdam, Netherlands
3.Key Lab Immun & Inflammatory Dis Zhejiang Prov, Hangzhou 310058, Zhejiang, Peoples R China
4.Chinese Acad Sci, Cryoelectron Microscopy Res Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
5.SARomics Biostruct AB, Scheelevagen 2, S-22363 Lund, Sweden
6.Univ Copenhagen, Dept Drug Design & Pharmacol, Univ Parken 2, DK-2100 Copenhagen, Denmark
7.Zhejiang Univ, MOE Frontier Sci Ctr Brain Res & Brain Machine In, Brain Machine Integrat, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China
8.Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Pathol, Hangzhou 310058, Peoples R China
9.Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Pathol, Sch Med, Hangzhou 310058, Peoples R China
10.ShanghaiTech Univ, Schl Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式
GB/T 7714		 Huang, Sijie,Xu, Peiyu,Shen, Dan-Dan,et al. GPCRs steer G(i) and G(s) selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors[J]. MOLECULAR CELL,2022,82(14):2681-+.
APA Huang, Sijie.,Xu, Peiyu.,Shen, Dan-Dan.,Simon, Icaro A..,Mao, Chunyou.,...&Xu, H. Eric.(2022).GPCRs steer G(i) and G(s) selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors.MOLECULAR CELL,82(14),2681-+.
MLA Huang, Sijie,et al."GPCRs steer G(i) and G(s) selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors".MOLECULAR CELL 82.14(2022):2681-+.

入库方式： OAI收割

来源：上海药物研究所

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