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Cryo-EM structures of human bradykinin receptor-G(q) proteins complexes
The type 2 bradykinin receptor (B2R) is a G protein-coupled receptor (GPCR) in the cardiovascular system, and the dysfunction of B2R leads to inflammation, hereditary angioedema, and pain. Bradykinin and kallidin are both endogenous peptide agonists of B2R, acting as vasodilators to protect the card...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821558/ https://www.ncbi.nlm.nih.gov/pubmed/35132089 http://dx.doi.org/10.1038/s41467-022-28399-1 |
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author | Shen, Jinkang Zhang, Dongqi Fu, Yao Chen, Anqi Yang, Xiaoli Zhang, Haitao |
author_facet | Shen, Jinkang Zhang, Dongqi Fu, Yao Chen, Anqi Yang, Xiaoli Zhang, Haitao |
author_sort | Shen, Jinkang |
collection | PubMed |
description | The type 2 bradykinin receptor (B2R) is a G protein-coupled receptor (GPCR) in the cardiovascular system, and the dysfunction of B2R leads to inflammation, hereditary angioedema, and pain. Bradykinin and kallidin are both endogenous peptide agonists of B2R, acting as vasodilators to protect the cardiovascular system. Here we determine two cryo-electron microscopy (cryo-EM) structures of human B2R-G(q) in complex with bradykinin and kallidin at 3.0 Å and 2.9 Å resolution, respectively. The ligand-binding pocket accommodates S-shaped peptides, with aspartic acids and glutamates as an anion trap. The phenylalanines at the tail of the peptides induce significant conformational changes in the toggle switch W283(6.48), the conserved PIF, DRY, and NPxxY motifs, for the B2R activation. This further induces the extensive interactions of the intracellular loops ICL2/3 and helix 8 with G(q) proteins. Our structures elucidate the molecular mechanisms for the ligand binding, receptor activation, and G(q) proteins coupling of B2R. |
format | Online Article Text |
id | pubmed-8821558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-88215582022-02-18 Cryo-EM structures of human bradykinin receptor-G(q) proteins complexes Shen, Jinkang Zhang, Dongqi Fu, Yao Chen, Anqi Yang, Xiaoli Zhang, Haitao Nat Commun Article The type 2 bradykinin receptor (B2R) is a G protein-coupled receptor (GPCR) in the cardiovascular system, and the dysfunction of B2R leads to inflammation, hereditary angioedema, and pain. Bradykinin and kallidin are both endogenous peptide agonists of B2R, acting as vasodilators to protect the cardiovascular system. Here we determine two cryo-electron microscopy (cryo-EM) structures of human B2R-G(q) in complex with bradykinin and kallidin at 3.0 Å and 2.9 Å resolution, respectively. The ligand-binding pocket accommodates S-shaped peptides, with aspartic acids and glutamates as an anion trap. The phenylalanines at the tail of the peptides induce significant conformational changes in the toggle switch W283(6.48), the conserved PIF, DRY, and NPxxY motifs, for the B2R activation. This further induces the extensive interactions of the intracellular loops ICL2/3 and helix 8 with G(q) proteins. Our structures elucidate the molecular mechanisms for the ligand binding, receptor activation, and G(q) proteins coupling of B2R. Nature Publishing Group UK 2022-02-07 /pmc/articles/PMC8821558/ /pubmed/35132089 http://dx.doi.org/10.1038/s41467-022-28399-1 Text en © The Author(s) 2022 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 Shen, Jinkang Zhang, Dongqi Fu, Yao Chen, Anqi Yang, Xiaoli Zhang, Haitao Cryo-EM structures of human bradykinin receptor-G(q) proteins complexes |
title | Cryo-EM structures of human bradykinin receptor-G(q) proteins complexes |
title_full | Cryo-EM structures of human bradykinin receptor-G(q) proteins complexes |
title_fullStr | Cryo-EM structures of human bradykinin receptor-G(q) proteins complexes |
title_full_unstemmed | Cryo-EM structures of human bradykinin receptor-G(q) proteins complexes |
title_short | Cryo-EM structures of human bradykinin receptor-G(q) proteins complexes |
title_sort | cryo-em structures of human bradykinin receptor-g(q) proteins complexes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821558/ https://www.ncbi.nlm.nih.gov/pubmed/35132089 http://dx.doi.org/10.1038/s41467-022-28399-1 |
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