Cargando…
Structural basis of peptide recognition and activation of 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 (ET(A)R) and B (ET(B)R). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothe...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992518/ https://www.ncbi.nlm.nih.gov/pubmed/36882417 http://dx.doi.org/10.1038/s41467-023-36998-9 |
_version_ | 1784902326959472640 |
---|---|
author | Ji, Yujie Duan, Jia Yuan, Qingning He, Xinheng Yang, Gong Zhu, Shengnan Wu, Kai Hu, Wen Gao, Tianyu Cheng, Xi Jiang, Hualiang Eric Xu, H. Jiang, Yi |
author_facet | Ji, Yujie Duan, Jia Yuan, Qingning He, Xinheng Yang, Gong Zhu, Shengnan Wu, Kai Hu, Wen Gao, Tianyu Cheng, Xi Jiang, Hualiang Eric Xu, H. Jiang, Yi |
author_sort | Ji, Yujie |
collection | PubMed |
description | 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 (ET(A)R) and B (ET(B)R). 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 ET(A)R and ET(B)R bound to ET-1 and ET(B)R 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. |
format | Online Article Text |
id | pubmed-9992518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99925182023-03-09 Structural basis of peptide recognition and activation of endothelin receptors Ji, Yujie Duan, Jia Yuan, Qingning He, Xinheng Yang, Gong Zhu, Shengnan Wu, Kai Hu, Wen Gao, Tianyu Cheng, Xi Jiang, Hualiang Eric Xu, H. Jiang, Yi Nat Commun Article 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 (ET(A)R) and B (ET(B)R). 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 ET(A)R and ET(B)R bound to ET-1 and ET(B)R 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. Nature Publishing Group UK 2023-03-07 /pmc/articles/PMC9992518/ /pubmed/36882417 http://dx.doi.org/10.1038/s41467-023-36998-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ji, Yujie Duan, Jia Yuan, Qingning He, Xinheng Yang, Gong Zhu, Shengnan Wu, Kai Hu, Wen Gao, Tianyu Cheng, Xi Jiang, Hualiang Eric Xu, H. Jiang, Yi Structural basis of peptide recognition and activation of endothelin receptors |
title | Structural basis of peptide recognition and activation of endothelin receptors |
title_full | Structural basis of peptide recognition and activation of endothelin receptors |
title_fullStr | Structural basis of peptide recognition and activation of endothelin receptors |
title_full_unstemmed | Structural basis of peptide recognition and activation of endothelin receptors |
title_short | Structural basis of peptide recognition and activation of endothelin receptors |
title_sort | structural basis of peptide recognition and activation of endothelin receptors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992518/ https://www.ncbi.nlm.nih.gov/pubmed/36882417 http://dx.doi.org/10.1038/s41467-023-36998-9 |
work_keys_str_mv | AT jiyujie structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT duanjia structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT yuanqingning structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT hexinheng structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT yanggong structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT zhushengnan structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT wukai structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT huwen structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT gaotianyu structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT chengxi structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT jianghualiang structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT ericxuh structuralbasisofpeptiderecognitionandactivationofendothelinreceptors AT jiangyi structuralbasisofpeptiderecognitionandactivationofendothelinreceptors |