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  2. 上海药物研究所
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  4. 新药研究国家重点实验室
Structural basis for hormone recognition and distinctive Gq protein coupling by the kisspeptin receptor

文献类型：期刊论文

作者Shen, Shiyi2,4; Wang, Dongxue3; Liu, Heng4; He, Xinheng2,4; Cao, Yinglong4; Chen, Juanhua4; Li, Shujie4; Cheng, Xi4; Xu, H. Eric1,2,4; Duan, Jia2,3,4
刊名CELL REPORTS
出版日期2024-07-23
卷号43期号:7页码:20
ISSN号2211-1247
DOI10.1016/j.celrep.2024.114389
通讯作者Xu, H. Eric(eric.xu@simm.ac.cn) ; Duan, Jia(duanjia@simm.ac.cn)
英文摘要Kisspeptin signaling through its G protein -coupled receptor, KISS1R, plays an indispensable role in regulating reproduction via the hypothalamic -pituitary -gonadal axis. Dysregulation of this pathway underlies severe disorders like infertility and precocious puberty. Here, we present cryo-EM structures of KISS1R bound to the endogenous agonist kisspeptin-10 and a synthetic analog TAK-448. These structures reveal pivotal interactions between peptide ligands and KISS1R extracellular loops for receptor activation. Both peptides exhibit a conserved binding mode, unveiling their common activation mechanism. Intriguingly, KISS1R displays a distinct 40 degrees angular deviation in its intracellular TM6 region compared to other G q -coupled receptors, enabling distinct interactions with G q . This study reveals the molecular intricacies governing ligand binding and activation of KISS1R, while highlighting its exceptional ability to couple with G q . Our findings pave the way for structure -guided design of therapeutics targeting this physiologically indispensable receptor.
WOS关键词FORCE-FIELD ; GPR54 ; SYSTEM ; METASTIN ; ANALOGS ; ROLES ; HYPOGONADISM ; TESTOSTERONE ; PEPTIDES ; SOFTWARE
资助项目CAS Strategic Priority Research Program[XDB37030103] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[82373881] ; Lingang Laboratory[LG-GG-202204-01] ; National Key R&D Program of China[2022YFC2703105] ; Young Elite Scientists Sponsorship Program by CAST[2022QNRC001] ; Shanghai Sailing Program[23YF1456800] ; Youth Innovation Promotion Association of Chinese Academy of Sciences
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:001261506100001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/312137]  
专题新药研究国家重点实验室
通讯作者Xu, H. Eric; Duan, Jia
作者单位1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Shen, Shiyi,Wang, Dongxue,Liu, Heng,et al. Structural basis for hormone recognition and distinctive Gq protein coupling by the kisspeptin receptor[J]. CELL REPORTS,2024,43(7):20.
APA Shen, Shiyi.,Wang, Dongxue.,Liu, Heng.,He, Xinheng.,Cao, Yinglong.,...&Duan, Jia.(2024).Structural basis for hormone recognition and distinctive Gq protein coupling by the kisspeptin receptor.CELL REPORTS,43(7),20.
MLA Shen, Shiyi,et al."Structural basis for hormone recognition and distinctive Gq protein coupling by the kisspeptin receptor".CELL REPORTS 43.7(2024):20.

入库方式： OAI收割

来源：上海药物研究所

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