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Structural insights into the ligand binding and G(i) coupling of serotonin receptor 5-HT5A

文献类型：期刊论文

作者Tan, Yangxia5,6; Xu, Peiyu4,6; Huang, Sijie5,6; Yang, Gong3; Zhou, Fulai4,6; He, Xinheng4,6; Ma, Honglei2; Xu, H. Eric4,5,6; Jiang, Yi1,5,6
刊名CELL DISCOVERY
出版日期2022-05-24
卷号8期号:1页码:9
DOI10.1038/s41421-022-00412-3
通讯作者Xu, H. Eric(eric.xu@simm.ac.cn) ; Jiang, Yi(yijiang@simm.ac.cn)
英文摘要5-hydroxytryptamine receptor 5A (5-HT5A) belongs to the 5-HT receptor family and signals through the G(i/o) protein. It is involved in nervous system regulation and an attractive target for the treatment of psychosis, depression, schizophrenia, and neuropathic pain. 5-HT5A is the only G(i/o)-coupled 5-HT receptor subtype lacking a high-resolution structure, which hampers the mechanistic understanding of ligand binding and G(i/o) coupling for 5-HT5A. Here we report a cryo-electron microscopy structure of the 5-HT5A-G(i) complex bound to 5-Carboxamidotryptamine (5-CT). Combined with functional analysis, this structure reveals the 5-CT recognition mechanism and identifies the receptor residue at 6.55 as a determinant of the 5-CT selectivity for G(i/o)-coupled 5-HT receptors. In addition, 5-HT5A shows an overall conserved G(i) protein coupling mode compared with other G(i/o)-coupled 5-HT receptors. These findings provide comprehensive insights into the ligand binding and G protein coupling of G(i/o)-coupled 5-HT receptors and offer a template for the design of 5-HT5A-selective drugs.
WOS关键词ANIMAL-MODELS ; AGONIST ; CLONING ; RECOGNITION ; SELECTIVITY ; VALIDATION ; ANTAGONIST
资助项目National Natural Science Foundation[32171187] ; National Natural Science Foundation[82121005] ; National Natural Science Foundation[32130022] ; Ministry of Science and Technology (China)[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; CAS Strategic Priority Research Program[XDB37030103] ; Shandong University[62450082163091] ; Shanghai Municipal Science and Technology Commission[19ZR1467500] ; Young Innovator Association of CAS Enrollment ; Shanghai Municipal Science and Technology Major Project
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000801185400001
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/301286]  
专题中国科学院上海药物研究所
通讯作者Xu, H. Eric; Jiang, Yi
作者单位1.Lingang Lab, Shanghai, Peoples R China
2.Shandong Univ, State Key Lab Microbial Technol, Qingdao, Shandong, Peoples R China
3.Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen, Fujian, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Medica, CAS Key Lab Receptor Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Tan, Yangxia,Xu, Peiyu,Huang, Sijie,et al. Structural insights into the ligand binding and G(i) coupling of serotonin receptor 5-HT5A[J]. CELL DISCOVERY,2022,8(1):9.
APA Tan, Yangxia.,Xu, Peiyu.,Huang, Sijie.,Yang, Gong.,Zhou, Fulai.,...&Jiang, Yi.(2022).Structural insights into the ligand binding and G(i) coupling of serotonin receptor 5-HT5A.CELL DISCOVERY,8(1),9.
MLA Tan, Yangxia,et al."Structural insights into the ligand binding and G(i) coupling of serotonin receptor 5-HT5A".CELL DISCOVERY 8.1(2022):9.

入库方式： OAI收割

来源：上海药物研究所

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