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Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor

文献类型：期刊论文

作者Wang, Yue1,2; Guo, Shimeng3,4; Zhuang, Youwen1; Yun, Ying2,4; Xu, Peiyu1,2; He, Xinheng1,2; Guo, Jia1,2; Yin, Wanchao1; Xu, H. Eric1,2,3,5; Xie, Xin2,3,4,5,6
刊名NATURE COMMUNICATIONS
出版日期2021-08-20
卷号12期号:1页码:9
ISSN号2041-1723
DOI10.1038/s41467-021-25364-2
通讯作者Xu, H. Eric(eric.xu@simm.ac.cn) ; Xie, Xin(xxie@simm.ac.cn) ; Jiang, Yi(yijiang@simm.ac.cn)
英文摘要Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of G(q)-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor. Ghrelin is a gastric peptide hormone and its acylation is required for binding to and activation of the ghrelin receptor in the brain, which initiates appetite. Here, the authors present cryo-EM structures of the G(q)-coupled ghrelin receptor bound to ghrelin and the synthetic agonist GHRP-6 and they describe how the acylated peptide hormone is recognised by the receptor, which is of interest for drug design.
WOS关键词CONSTITUTIVE ACTIVITY ; SECRETAGOGUE RECEPTOR ; CRYSTAL-STRUCTURE ; IDENTIFICATION ; VALIDATION ; LEPTIN
资助项目National Natural Science Foundation[31770796] ; National Natural Science Foundation[81730099] ; National Science and Technology Major Project[2018ZX09711002-002-002] ; National Key R&D Programs of China[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; CAS Strategic Priority Research Program[XDB37030103] ; Shanghai Municipal Science and Technology Commission[20S11903200]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000687171500007
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/297958]  
专题中国科学院上海药物研究所
通讯作者Xu, H. Eric; Xie, Xin; Jiang, Yi
作者单位1.Chinese Acad Sci, Ctr Struct & Funct Drug Targets, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China
4.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
6.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Yue,Guo, Shimeng,Zhuang, Youwen,et al. Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor[J]. NATURE COMMUNICATIONS,2021,12(1):9.
APA Wang, Yue.,Guo, Shimeng.,Zhuang, Youwen.,Yun, Ying.,Xu, Peiyu.,...&Jiang, Yi.(2021).Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor.NATURE COMMUNICATIONS,12(1),9.
MLA Wang, Yue,et al."Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor".NATURE COMMUNICATIONS 12.1(2021):9.

入库方式： OAI收割

来源：上海药物研究所

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