Ligand recognition and activation of neuromedin U receptor 2

doi:10.1038/s41467-022-34814-4

	Ligand recognition and activation of neuromedin U receptor 2
	Zhao, Wenli 1,2,3; Zhang, Wenru 4; Wang, Mu1,2,5 ; Lu, Minmin 1,2,3; Chen, Shutian 1,2,3; Tang, Tingting 1,2,3; Schnapp, Gisela 6; Wagner, Holger 6; Brennauer, Albert 6; Yi, Cuiying 1,2; Chu, Xiaojing 1,2; Han, Shuo 1,2,7; Wu, Beili 2,3,7; Zhao, Qiang 1,3,4,8
	2022-12-27
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	13 期号:1
发表状态	已发表
DOI	10.1038/s41467-022-34814-4
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."]
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收录类别	SCI
语种	英语
资助项目	National Key R&D Program of China[2018YFA0507000] ; CAS Strategic Priority Research Program[XDB37030100] ; National Science Foundation of China["31825010","82121005"]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000935585400014
出版者	NATURE PORTFOLIO
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/284218
专题	生命科学与技术学院_博士生
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).
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).
MLA	Zhao, Wenli,et al."Ligand recognition and activation of neuromedin U receptor 2".NATURE COMMUNICATIONS 13.1(2022).