Structural insights into hormone recognition and G-protein coupling of the urotensin-II receptor
文献类型：期刊论文
| 作者 | Gao, Tianyu2,3; You, Chongzhao3; Cao, Yinglong1; Xu, Xiaofang4; Yuan, Qingning5; Shen, Shiyi3; Xu, H. Eric2,3; Duan, Jia1,3 |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2025-11-01 |
| 卷号 | 301期号:11页码:11 |
| DOI | 10.1016/j.jbc.2025.110794 |
| 英文摘要 | Urotensin-II (U-II) is a potent vasoconstrictor peptide that interacts with the human urotensin-II receptor (UTR), a class A G protein-coupled receptor (GPCR) that primarily couples with Gq proteins. In this study, we present the cryo-electron microscopy structure of the miniGq-coupled UTR bound to the potent UTR agonist P5U, providing insights into unique ligand recognition and activation mechanisms. Unlike typical linear peptides, the cyclic structure of P5U engages the receptor's transmembrane domains through key side chain interactions involving residues F6, W7, K8, and Y9, which are crucial for receptor activation. Comparative analysis with somatostatin receptors (SSTRs) reveals distinct ligand specificity, driven by variations in side chain composition. Notably, we identify F274 6.51 as the toggle switch residue in UTR, in contrast to the classical W 6.48 seen in other GPCRs. Our findings elucidate the structural basis for UTR's Gq coupling specificity, highlighting unique G alpha q interactions. This study advances the understanding of U-II signaling and offers a foundation for developing selective UTR modulators, with potential therapeutic implications for cardiovascular diseases linked to dysregulated U-II activity. |
| WOS关键词 | ANTAGONIST PALOSURAN ; ORPHAN-RECEPTOR ; ENDOGENOUS LIGAND ; PEPTIDE ; VASOCONSTRICTOR ; MODEL ; IDENTIFICATION ; AGONIST ; SYSTEM ; HEALTH |
| 资助项目 | National Natural Science Foundation of China[82373881] ; National Natural Science Foundation of China[32130022] ; National Natural Science Foundation of China[82121005] ; Young Elite Scientists Sponsorship Program by CAST[2022QNRC001] ; Shanghai Sailing Program[23YF1456800] ; Youth Innovation Promotion Association of Chinese Academy of Sciences ; Lingang Laboratory[LG-8888] ; CAS Strategic Priority Research Program[XDB37030103] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Shanghai Municipal Science and Technology Major Project ; Lingang Laboratory[LG-GG-202204-01] ; National Key R&D Program of China[2022YFC2703105] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001613124500007 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321742]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Xu, H. Eric; Duan, Jia |
| 作者单位 | 1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China 4.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou, Peoples R China 5.Nanjing Univ Chinese Med, Coll Pharm, Nanjing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Tianyu,You, Chongzhao,Cao, Yinglong,et al. Structural insights into hormone recognition and G-protein coupling of the urotensin-II receptor[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2025,301(11):11. |
| APA | Gao, Tianyu.,You, Chongzhao.,Cao, Yinglong.,Xu, Xiaofang.,Yuan, Qingning.,...&Duan, Jia.(2025).Structural insights into hormone recognition and G-protein coupling of the urotensin-II receptor.JOURNAL OF BIOLOGICAL CHEMISTRY,301(11),11. |
| MLA | Gao, Tianyu,et al."Structural insights into hormone recognition and G-protein coupling of the urotensin-II receptor".JOURNAL OF BIOLOGICAL CHEMISTRY 301.11(2025):11. |
入库方式： OAI收割
来源：上海药物研究所
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