Structural insights into the peptide selectivity and activation of human neuromedin U receptors
文献类型：期刊论文
| 作者 | You, Chongzhao1,2; Zhang, Yumu1,3; Xu, Peiyu1,2; Huang, Sijie1,3; Yin, Wanchao1; Xu, H. Eric1,2,3 ; Jiang, Yi1,3,4
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| 刊名 | NATURE COMMUNICATIONS
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| 出版日期 | 2022-04-19 |
| 卷号 | 13期号:1页码:10 |
| DOI | 10.1038/s41467-022-29683-w |
| 通讯作者 | Xu, H. Eric(eric.xu@simm.ac.cn) ; Jiang, Yi(yijiang@simm.ac.cn) |
| 英文摘要 | Neuromedin U receptors (NMURs), including NMUR1 and NMUR2, are a group of G(q/11)-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(q) 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. Neuromedin U receptors (NMURs) are potential drug targets for obesity and inflammatory disorders. Here, the authors report structural basis for neuromedin recognition and activation mechanism of NMURs. |
| 资助项目 | National Natural Science Foundation[32171187] ; National Natural Science Foundation[82121005] ; National Natural Science Foundation[32130022] ; Ministry of Science and Technology (China)[2018YFA0507002] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; CAS Strategic Priority Research Program[XDB37030103] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PORTFOLIO |
| WOS记录号 | WOS:000784997300075 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299292]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, H. Eric; Jiang, Yi |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.Lingang Lab, Shanghai 200031, Peoples R China |
| 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):10. |
| 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),10. |
| MLA | You, Chongzhao,et al."Structural insights into the peptide selectivity and activation of human neuromedin U receptors".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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