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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
Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor

文献类型：期刊论文

作者Li, Yang3,4; Yuan, Qingning2; He, Xinheng3,4; Zhang, Yumu4; You, Chongzhao3,4; Wu, Canrong4; Li, Jingru2,4; Xu, H. Eric3,4; Zhao, Li-Hua1,3,4
刊名CELL DISCOVERY
出版日期2024-09-03
卷号10期号:1页码:12
DOI10.1038/s41421-024-00724-6
通讯作者Xu, H. Eric(eric.xu@simm.ac.cn) ; Zhao, Li-Hua(zhaolihuawendy@simm.ac.cn)
英文摘要Prolactin-releasing peptide (PrRP) is an RF-amide neuropeptide that binds and activates its cognate G protein-coupled receptor, prolactin-releasing peptide receptor (PrRPR), also known as GPR10. PrRP and PrRPR are highly conserved across mammals and involved in regulating a range of physiological processes, including stress response, appetite regulation, pain modulation, cardiovascular function, and potentially reproductive functions. Here we present cryo-electron microscopy structures of PrRP-bound PrRPR coupled to Gq or Gi heterotrimer, unveiling distinct molecular determinants underlying the specific recognition of the ligand's C-terminal RF-amide motif. We identify a conserved polar pocket that accommodates the C-terminal amide shared by RF-amide peptides. Structural comparison with neuropeptide Y receptors reveals both similarities and differences in engaging the essential RF/RY-amide motifs. Our findings demonstrate the general mechanism governing RF-amide motif recognition by PrRPR and RF-amide peptide receptors, and provide a foundation for elucidating activation mechanisms and developing selective drugs targeting this important peptide-receptor system.
WOS关键词CENTRAL-NERVOUS-SYSTEM ; NEUROPEPTIDE ; ACTIVATION ; DYNAMICS ; PRRP ; IDENTIFICATION ; ANALOGS ; 26RFA ; PAIN ; FF
资助项目National Natural Science Foundation of China (32371255, 32071203 to L.H.Z., 32130022 and 82121005 to H.E.X.); Natural Science Foundation of Shanghai (23ZR1475200 to L.H.Z.); the National Key RD Program of China (2022YFC2703105 to H.E.X., 2019YFA0904200); ; Chinese Academy of Sciences[2022YFC2703105] ; Chinese Academy of Sciences[2019YFA0904200] ; National Key R&D Program of China[32371255] ; National Key R&D Program of China[32071203] ; National Key R&D Program of China[32130022] ; National Key R&D Program of China[82121005] ; National Natural Science Foundation of China[23ZR1475200] ; Natural Science Foundation of Shanghai[XDB37030103] ; CAS Strategic Priority Research Program[2019SHZDZX02] ; Shanghai Municipal Science and Technology Major Project[Y2022078] ; Shanghai Municipal Science and Technology Major Project[LG-GG-202204-01] ; Young Innovator Association of CAS[SKLDR-2023-TT-04] ; State Key Laboratory of Drug Research
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:001304061300002
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/313083]  
专题新药研究国家重点实验室
通讯作者Xu, H. Eric; Zhao, Li-Hua
作者单位1.Shanghai Jiao Tong Univ, Ruijin Hosp, Translat Ctr Med Struct Biol, Sch Med, Shanghai, Peoples R China
2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Jiangsu, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Struct & Funct Drug Targets, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Li, Yang,Yuan, Qingning,He, Xinheng,et al. Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor[J]. CELL DISCOVERY,2024,10(1):12.
APA Li, Yang.,Yuan, Qingning.,He, Xinheng.,Zhang, Yumu.,You, Chongzhao.,...&Zhao, Li-Hua.(2024).Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor.CELL DISCOVERY,10(1),12.
MLA Li, Yang,et al."Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor".CELL DISCOVERY 10.1(2024):12.

入库方式： OAI收割

来源：上海药物研究所

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