Structural insights into the peptide selectivity and activation of human neuromedin U receptors

doi:10.1038/s41467-022-29683-w

	Structural insights into the peptide selectivity and activation of human neuromedin U receptors
	You, Chongzhao 1,2; Zhang, Yumu1,3 ; Xu, Peiyu 1,2; Huang, Sijie1,3 ; Yin, Wanchao 1; Eric Xu, H.1,2,3 ; Jiang, Yi1,3,4
	2022-04-19
发表期刊	NATURE COMMUNICATIONS
EISSN	2041-1723
卷号	13 期号:1
发表状态	已发表
DOI	10.1038/s41467-022-29683-w
摘要	Neuromedin U receptors (NMURs), including NMUR1 and NMUR2, are a group of G-coupled G protein-coupled receptors (GPCRs). NMUR1 and NMUR2 play distinct, pleiotropic physiological functions in peripheral tissues and in the central nervous system (CNS), respectively, according to their distinct tissue distributions. These receptors are stimulated by two endogenous neuropeptides, neuromedin U and S (NMU and NMS) with similar binding affinities. NMURs have gathered attention as potential drug targets for obesity and inflammatory disorders. Specifically, selective agonists for NMUR2 in peripheral tissue show promising long-term anti-obesity effects with fewer CNS-related side effects. However, the mechanisms of peptide binding specificity and receptor activation remain elusive. Here, we report four cryo-electron microscopy structures of G chimera-coupled NMUR1 and NMUR2 in complexes with NMU and NMS. These structures reveal the conserved overall peptide-binding mode and the mechanism of peptide selectivity for specific NMURs, as well as the common activation mechanism of the NMUR subfamily. Together, these findings provide insights into the molecular basis of the peptide recognition and offer an opportunity for the design of the selective drugs targeting NMURs.
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收录类别	SCIE
语种	英语
Scopus 记录号	2-s2.0-85128411863
来源库	Scopus
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/176066
专题	生命科学与技术学院_博士生生命科学与技术学院生命科学与技术学院_特聘教授组_徐华强组
通讯作者	Eric Xu, H.; Jiang, Yi
作者单位	1.The CAS Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China 2.University of Chinese Academy of Sciences,Beijing,100049,China 3.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China 4.Lingang Laboratory,Shanghai,200031,China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	You, Chongzhao,Zhang, Yumu,Xu, Peiyu,et al. Structural insights into the peptide selectivity and activation of human neuromedin U receptors[J]. NATURE COMMUNICATIONS,2022,13(1).
APA	You, Chongzhao.,Zhang, Yumu.,Xu, Peiyu.,Huang, Sijie.,Yin, Wanchao.,...&Jiang, Yi.(2022).Structural insights into the peptide selectivity and activation of human neuromedin U receptors.NATURE COMMUNICATIONS,13(1).
MLA	You, Chongzhao,et al."Structural insights into the peptide selectivity and activation of human neuromedin U receptors".NATURE COMMUNICATIONS 13.1(2022).