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Ligand recognition and activation of neuromedin U receptor 2

文献类型：期刊论文

作者Zhao, Wenli1,2,3; Zhang, Wenru4; Wang, Mu1,2,5; Lu, Minmin1,2,3; Chen, Shutian1,2,3; Tang, Tingting1,2,3; Schnapp, Gisela6; Wagner, Holger6; Brennauer, Albert6; Yi, Cuiying1,2
刊名NATURE COMMUNICATIONS
出版日期2022-12-27
卷号13期号:1页码:7955
DOI10.1038/s41467-022-34814-4
文献子类Article
英文摘要Neuromedin U receptor 2 is an emerging attractive target for treating obesity. Here, a Cryo-EM structure of NmU-25-NMU2-G(i1) provides the structural basis for the designation of highly selective drugs. Neuromedin U receptor 2 (NMU2), an emerging attractive target for treating obesity, has shown the capability in reducing food intake and regulating energy metabolism when activated. However, drug development of NMU2 was deferred partially due to the lack of structural information. Here, we present the cryo-electron microscopy (cryo-EM) structure of NMU2 bound to the endogenous agonist NmU-25 and G(i1) at 3.3 angstrom resolution. Combined with functional and computational data, the structure reveals the key factors that govern the recognition and selectivity of peptide agonist as well as non-peptide antagonist, providing the structural basis for design of novel and highly selective drugs targeting NMU2. In addition, a 25-degree rotation of G(i) protein in reference to NMU2 is also observed compared in other structures of class A GPCR-G(i) complexes, suggesting heterogeneity in the processes of G protein-coupled receptors (GPCRs) activation and G protein coupling.
WOS关键词STRUCTURAL BASIS ; G-PROTEINS ; AGONIST ; IDENTIFICATION ; NEUROPEPTIDE ; DISCOVERY ; RESPONSES ; SYSTEM
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:000935585400014
源URL[http://119.78.100.183/handle/2S10ELR8/309295]  
专题新药研究国家重点实验室
通讯作者Han, Shuo; Wu, Beili; Zhao, Qiang
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd,Pudong, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;
3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China;
4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China;
5.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Hua Xia Zhong Rd, Pudong, Shanghai 201210, Peoples R China;
6.Boehringer Ingelheim Pharm GmbH & Co, Dept Med Chem, KG, Birkendorfer Str 65, D-88397 Biberach, Germany;
7.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China;
8.Chinese Acad Sci, Inst Drug Discovery & Dev, Zhongshan Branch, Zhongshan, Peoples R China
推荐引用方式
GB/T 7714		 Zhao, Wenli,Zhang, Wenru,Wang, Mu,et al. Ligand recognition and activation of neuromedin U receptor 2[J]. NATURE COMMUNICATIONS,2022,13(1):7955.
APA Zhao, Wenli.,Zhang, Wenru.,Wang, Mu.,Lu, Minmin.,Chen, Shutian.,...&Zhao, Qiang.(2022).Ligand recognition and activation of neuromedin U receptor 2.NATURE COMMUNICATIONS,13(1),7955.
MLA Zhao, Wenli,et al."Ligand recognition and activation of neuromedin U receptor 2".NATURE COMMUNICATIONS 13.1(2022):7955.

入库方式： OAI收割

来源：上海药物研究所

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