Structural basis of peptide recognition and activation of endothelin receptors
文献类型：期刊论文
| 作者 | Ji, Yujie2,3; Duan, Jia2,3,4; Yuan, Qingning2; He, Xinheng2,3; Yang, Gong5; Zhu, Shengnan6; Wu, Kai2; Hu, Wen2; Gao, Tianyu1; Cheng, Xi2,3 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2023-03-07 |
| 卷号 | 14期号:1页码:9 |
| DOI | 10.1038/s41467-023-36998-9 |
| 通讯作者 | Duan, Jia(duanjia@simm.ac.cn) ; Xu, H. Eric(eric.xu@simm.ac.cn) ; Jiang, Yi(yjiang@lglab.ac.cn) |
| 英文摘要 | Endothelin receptors (ETAR and ETBR) are critical for vasoregulation and are targets for cardiovascular diseases treatment. Here, the authors offer a structural basis for peptide recognition selectivity and activation of both endothelin receptors. Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ETAR) and B (ETBR). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothelial cell-derived vasoconstrictor peptides with long-lasting actions, the endothelin system has attracted extensive attention due to its critical role in vasoregulation and close relevance in cardiovascular-related diseases. Here we present three cryo-electron microscopy structures of ETAR and ETBR bound to ET-1 and ETBR bound to the selective peptide IRL1620. These structures reveal a highly conserved recognition mode of ET-1 and characterize the ligand selectivity by ETRs. They also present several conformation features of the active ETRs, thus revealing a specific activation mechanism. Together, these findings deepen our understanding of endothelin system regulation and offer an opportunity to design selective drugs targeting specific ETR subtypes. |
| WOS关键词 | ETB-RECEPTOR ; VASOCONSTRICTOR PEPTIDE ; CRYSTAL-STRUCTURE ; PHARMACOLOGY ; SYSTEM ; SARAFOTOXIN ; PHYSIOLOGY ; CLONING ; POTENT ; SCAN |
| 资助项目 | National Natural Science Foundation ; Ministry of Science and Technology (China) ; Shanghai Municipal Science and Technology Major Project ; Shanghai Municipal Science and Technology Major Project ; CAS Strategic Priority Research Program ; [32171187] ; [82121005] ; [32130022] ; [2018YFA0507002] ; [2019SHZDZX02] ; [XDB37030103] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000957599200017 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306554]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Duan, Jia; Xu, H. Eric; Jiang, Yi |
| 作者单位 | 1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Zhongshan Inst Drug Discovery, Zhongshan, Peoples R China 5.Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China 6.Macau Univ Sci & Technol, Sch Pharm, Macau 999078, Peoples R China 7.Lingang Lab, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ji, Yujie,Duan, Jia,Yuan, Qingning,et al. Structural basis of peptide recognition and activation of endothelin receptors[J]. NATURE COMMUNICATIONS,2023,14(1):9. |
| APA | Ji, Yujie.,Duan, Jia.,Yuan, Qingning.,He, Xinheng.,Yang, Gong.,...&Jiang, Yi.(2023).Structural basis of peptide recognition and activation of endothelin receptors.NATURE COMMUNICATIONS,14(1),9. |
| MLA | Ji, Yujie,et al."Structural basis of peptide recognition and activation of endothelin receptors".NATURE COMMUNICATIONS 14.1(2023):9. |
入库方式： OAI收割
来源：上海药物研究所
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