Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor

doi:10.1038/s41421-024-00670-3

	Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor
	Jin, Sanshan 1; Guo, Shimeng 2; Xu, Youwei 2; Li, Xin 2,3; Wu, Canrong 2; He, Xinheng 2,3; Pan, Benxun 1; Xin, Wenwen 2,3,4; Zhang, Heng 2; Hu, Wen 2,5; Yin, Yuling 1; Zhang, Tianwei1,6 ; Wu, Kai 2,5; Yuan, Qingning 2,5; Xu, H. Eric 2,3,5; Xie, Xin2,3,4,6,7 ; Jiang, Yi1,6
	2024-06-04
发表期刊	CELL DISCOVERY (IF:13.0[JCR-2023],14.8[5-Year])
EISSN	2056-5968
卷号	10 期号:1
发表状态	已发表
DOI	10.1038/s41421-024-00670-3
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.
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收录类别	SCI
语种	英语
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","82121005","82330113","32130022","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","2022232"] ; Shanghai Sailing Program["23YF1460700","22YF1461200"]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:001238231000002
出版者	SPRINGERNATURE
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/387275
专题	生命科学与技术学院_博士生生命科学与技术学院生命科学与技术学院_特聘教授组_谢欣组
通讯作者	Xu, H. Eric; Xie, Xin; Jiang, Yi
作者单位	1.Lingang Lab, Shanghai, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Zhejiang, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Adv Electron Microscope Ctr, Shanghai, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 7.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Shandong, Peoples R China
通讯作者单位	生命科学与技术学院
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).
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).
MLA	Jin, Sanshan,et al."Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor".CELL DISCOVERY 10.1(2024).