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A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2

文献类型：期刊论文

作者Xu, Yingna3; Feng, Wenbo3; Zhou, Qingtong3; Liang, Anyi4; Li, Jie3; Dai, Antao5; Zhao, Fenghui5; Yan, Jiahui5,6,7; Chen, Chuan-Wei1; Li, Hao1
刊名NATURE COMMUNICATIONS
出版日期2022-04-27
卷号13期号:1页码:10
DOI10.1038/s41467-022-30041-z
通讯作者Xu, H. Eric(eric.xu@simm.ac.cn) ; Yang, Dehua(dhyang@simm.ac.cn) ; Wang, Ming-Wei(mwwang@simm.ac.cn)
英文摘要Class B1 of G protein-coupled receptors (GPCRs) comprises 15 members activated by physiologically important peptide hormones. Among them, vasoactive intestinal polypeptide receptor 2 (VIP2R) is expressed in the central and peripheral nervous systems and involved in a number of pathophysiological conditions, including pulmonary arterial hypertension, autoimmune and psychiatric disorders, in which it is thus a valuable drug target. Here, we report the cryo-electron microscopy structure of the human VIP2R bound to its endogenous ligand PACAP27 and the stimulatory G protein. Different from all reported peptide-bound class B1 GPCR structures, the N-terminal alpha-helix of VIP2R adopts a unique conformation that deeply inserts into a cleft between PACAP27 and the extracellular loop 1, thereby stabilizing the peptide-receptor interface. Its truncation or extension significantly decreased VIP2R-mediated cAMP accumulation. Our results provide additional information on peptide recognition and receptor activation among class B1 GPCRs and may facilitate the design of better therapeutics. Vasoactive intestinal polypeptide receptor 2 (VIP2R) is involved in immunity. Here, the authors report two cryo-EM structures of the VIP2R-G(s) in complex with the endogenous peptide ligand PACAP27, revealing a unique interaction mode between PACAP27 and the receptor, stabilized by the N-terminal alpha-helix of VIP2R.
WOS关键词CYCLASE-ACTIVATING POLYPEPTIDE ; CRYO-EM STRUCTURE ; PEPTIDE ; DYNAMICS ; BINDING ; TISSUES
资助项目National Natural Science Foundation of China[81872915] ; National Natural Science Foundation of China[82073904] ; National Natural Science Foundation of China[81773792] ; National Natural Science Foundation of China[81973373] ; National Natural Science Foundation of China[21704064] ; National Science & Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09735-001] ; National Science & Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09711002-002-005] ; National Science & Technology Major Project of China - Innovation 2030 for Brain Science and Brain-Inspired Technology[2021ZD0203400] ; National Key Basic Research Program of China[2018YFA0507000] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Ministry of Science and Technology of China Major Project[XDB08020303] ; Novo Nordisk-CAS Research Fund[NNCAS-2017-1-CC] ; Young Innovator Association of CAS Enrollment ; SA-SIBS Scholarship Program
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:000788592600011
源URL[http://119.78.100.183/handle/2S10ELR8/299393]  
专题中国科学院上海药物研究所
通讯作者Xu, H. Eric; Yang, Dehua; Wang, Ming-Wei
作者单位1.Res Ctr Deepsea Bioresources, Sanya 572025, Hainan, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
3.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai 200032, Peoples R China
4.Huazhong Univ Sci & Technol, Sch Artificial Intelligence & Automat, Wuhan 430074, Peoples R China
5.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
8.Univ Tokyo, Sch Sci, Dept Chem, Tokyo 1130033, Japan
推荐引用方式
GB/T 7714		 Xu, Yingna,Feng, Wenbo,Zhou, Qingtong,et al. A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2[J]. NATURE COMMUNICATIONS,2022,13(1):10.
APA Xu, Yingna.,Feng, Wenbo.,Zhou, Qingtong.,Liang, Anyi.,Li, Jie.,...&Wang, Ming-Wei.(2022).A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2.NATURE COMMUNICATIONS,13(1),10.
MLA Xu, Yingna,et al."A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2".NATURE COMMUNICATIONS 13.1(2022):10.

入库方式： OAI收割

来源：上海药物研究所

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