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  5. 原创新药研究全国重点实验室
Molecular basis for cross-activation of NPFF2R by a short PrRP-related peptide

文献类型：期刊论文

作者Li, Xin4,5; Li, Shuai5; Shan, Hong5; Yuan, Qing-ning3; He, Xin-heng2; He, Qian4,5; Zhang, Min4,5; Li, Yang1,5; Hu, Wen5; Wu, Kai5
刊名ACTA PHARMACOLOGICA SINICA
出版日期2026-02-04
页码11
关键词prolactin-releasing peptide PrRPR NPFF2R ligand recognition obesity therapy
ISSN号1671-4083
DOI10.1038/s41401-025-01741-1
英文摘要Prolactin-releasing peptide (PrRP) is an endogenous ligand for the PrRPR, whose activation has been linked to anti-obesity effects. However, PrRP and its analogs also activate the neuropeptide FF receptor 2 (NPFF2R), which is associated with adverse cardiovascular effects. Understanding how PrRP-related peptides differentially engage these two distinct receptors is critical for developing safer, more selective therapeutics. In this study, we present cryo-EM structures of the PrRP analog GUB08248 bound to PrRPR-G alpha q and NPFF2R-G alpha i at resolutions of 2.45 & Aring; and 2.85 & Aring;, respectively. These structures reveal a conserved ligand recognition mode across both receptors, while highlighting distinct receptor-specific interactions. The NPFF2R-G alpha i complex further uncovers key features of receptor activation and G protein coupling. Together, our results offer structural insights that could guide structure-based drug design strategies favoring PrRPR selectivity, thereby advancing the therapeutic potential of the PrRP-PrRPR axis for obesity treatment.
WOS关键词PROLACTIN-RELEASING PEPTIDE ; IMPROVES GLYCEMIC CONTROL ; LOWERS BODY-WEIGHT ; NEUROPEPTIDE FF ; RECEPTOR GPR10 ; FOOD-INTAKE ; HORMONE ; DYNAMICS ; ADRENOCORTICOTROPIN ; LIRAGLUTIDE
资助项目Chinese Academy of Sciences ; National Natural Science Foundation of China[32371255] ; National Natural Science Foundation of China[32071203] ; National Natural Science Foundation of China[82495184] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[82404881] ; Natural Science Foundation of Shanghai[23ZR1475200] ; National Key R&D Program of China[2022YFC2703105] ; CAS Strategic Priority Research Program[XDB37030103] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Young Innovator Association of CAS[Y2022078] ; Young Innovator Association of CAS[LG-GG-202204-01] ; State Key Laboratory of Drug Research[SKLDR-2023-TT-04]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001679722100001
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/322752]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Xu, H. Eric; Zhao, Li-hua
作者单位1.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
2.Lingang Lab, Shanghai 201100, Peoples R China
3.Shanghai Jiao Tong Univ, Res Ctr Med Struct Biol, Natl Res Ctr Translat Med Shanghai, State Key Lab Med Genom,Ruijin Hosp Affiliated,Sch, Shanghai 200025, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.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		 Li, Xin,Li, Shuai,Shan, Hong,et al. Molecular basis for cross-activation of NPFF2R by a short PrRP-related peptide[J]. ACTA PHARMACOLOGICA SINICA,2026:11.
APA Li, Xin.,Li, Shuai.,Shan, Hong.,Yuan, Qing-ning.,He, Xin-heng.,...&Zhao, Li-hua.(2026).Molecular basis for cross-activation of NPFF2R by a short PrRP-related peptide.ACTA PHARMACOLOGICA SINICA,11.
MLA Li, Xin,et al."Molecular basis for cross-activation of NPFF2R by a short PrRP-related peptide".ACTA PHARMACOLOGICA SINICA (2026):11.

入库方式： OAI收割

来源：上海药物研究所

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