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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 recognition of 26RFa by the pyroglutamylated RFamide peptide receptor

文献类型：期刊论文

作者Jin, Sanshan7; Guo, Shimeng6; Xu, Youwei6; Li, Xin5,6; Wu, Canrong6; He, Xinheng5,6; Pan, Benxun7; Xin, Wenwen4,5,6; Zhang, Heng6; Hu, Wen3,6
刊名CELL DISCOVERY
出版日期2024-06-04
卷号10期号:1页码:13
DOI10.1038/s41421-024-00670-3
通讯作者Xu, H. Eric(eric.xu@simm.ac.cn) ; Xie, Xin(xxie@simm.ac.cn) ; Jiang, Yi(yjiang@lglab.ac.cn)
英文摘要The neuropeptide 26RFa, a member of the RF-amide peptide family, activates the pyroglutamylated RF-amide peptide receptor (QRFPR), a class A GPCR. The 26RFa/QRFPR system plays critical roles in energy homeostasis, making QRFPR an attractive drug target for treating obesity, diabetes, and eating disorders. However, the lack of structural information has hindered our understanding of the peptide recognition and regulatory mechanism of QRFPR, impeding drug design efforts. In this study, we determined the cryo-EM structure of the Gq-coupled QRFPR bound to 26RFa. The structure reveals a unique assembly mode of the extracellular region of the receptor and the N-terminus of the peptide, and elucidates the recognition mechanism of the C-terminal heptapeptide of 26RFa by the transmembrane binding pocket of QRFPR. The study also clarifies the similarities and distinctions in the binding pattern of the RF-amide moiety in five RF-amide peptides and the RY-amide segment in neuropeptide Y. These findings deepen our understanding of the RF-amide peptide recognition, aiding in the rational design of drugs targeting QRFPR and other RF-amide peptide receptors.
WOS关键词HYPOTHALAMIC NEUROPEPTIDE ; IN-VIVO ; LIGAND ; GPR103 ; IDENTIFICATION ; ACTIVATION ; BINDING ; SELECTIVITY ; FMRFAMIDE ; SOFTWARE
资助项目National Natural Science Foundation of China (National Science Foundation of China)[LG-GG-202204-01] ; National Natural Science Foundation of China[32171187] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[82330113] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82304579] ; CAS Strategic Priority Research Program[XDB37030103] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; China Postdoctoral Science Foundation[2023M731487] ; Shanghai Post-doctoral Excellence Program[2023018] ; Shanghai Post-doctoral Excellence Program[2022232] ; Shanghai Sailing Program[23YF1460700] ; Shanghai Sailing Program[22YF1461200]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:001238231000002
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/311594]  
专题新药研究国家重点实验室
通讯作者Xu, H. Eric; Xie, Xin; Jiang, Yi
作者单位1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Shandong, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Adv Electron Microscope Ctr, Shanghai, Peoples R China
4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Zhejiang, Peoples R China
5.Univ Chinese Acad Sci, Beijing, Peoples R China
6.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China
7.Lingang Lab, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Jin, Sanshan,Guo, Shimeng,Xu, Youwei,et al. Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor[J]. CELL DISCOVERY,2024,10(1):13.
APA Jin, Sanshan.,Guo, Shimeng.,Xu, Youwei.,Li, Xin.,Wu, Canrong.,...&Jiang, Yi.(2024).Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor.CELL DISCOVERY,10(1),13.
MLA Jin, Sanshan,et al."Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor".CELL DISCOVERY 10.1(2024):13.

入库方式： OAI收割

来源：上海药物研究所

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