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Coevolution underlies GPCR-G protein selectivity and functionality
G protein-coupled receptors (GPCRs) regulate diverse physiological events, which makes them as the major targets for many approved drugs. G proteins are downstream molecules that receive signals from GPCRs and trigger cell responses. The GPCR-G protein selectivity mechanism on how they properly and...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041822/ https://www.ncbi.nlm.nih.gov/pubmed/33846507 http://dx.doi.org/10.1038/s41598-021-87251-6 |
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author | Seo, Min Jae Heo, Joongyu Kim, Kyunghui Chung, Ka Young Yu, Wookyung |
author_facet | Seo, Min Jae Heo, Joongyu Kim, Kyunghui Chung, Ka Young Yu, Wookyung |
author_sort | Seo, Min Jae |
collection | PubMed |
description | G protein-coupled receptors (GPCRs) regulate diverse physiological events, which makes them as the major targets for many approved drugs. G proteins are downstream molecules that receive signals from GPCRs and trigger cell responses. The GPCR-G protein selectivity mechanism on how they properly and timely interact is still unclear. Here, we analyzed model GPCRs (i.e. HTR, DAR) and Gα proteins with a coevolutionary tool, statistical coupling analysis. The results suggested that 5-hydroxytryptamine receptors and dopamine receptors have common conserved and coevolved residues. The Gα protein also have conserved and coevolved residues. These coevolved residues were implicated in the molecular functions of the analyzed proteins. We also found specific coevolving pairs related to the selectivity between GPCR and G protein were identified. We propose that these results would contribute to better understandings of not only the functional residues of GPCRs and Gα proteins but also GPCR-G protein selectivity mechanisms. |
format | Online Article Text |
id | pubmed-8041822 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80418222021-04-13 Coevolution underlies GPCR-G protein selectivity and functionality Seo, Min Jae Heo, Joongyu Kim, Kyunghui Chung, Ka Young Yu, Wookyung Sci Rep Article G protein-coupled receptors (GPCRs) regulate diverse physiological events, which makes them as the major targets for many approved drugs. G proteins are downstream molecules that receive signals from GPCRs and trigger cell responses. The GPCR-G protein selectivity mechanism on how they properly and timely interact is still unclear. Here, we analyzed model GPCRs (i.e. HTR, DAR) and Gα proteins with a coevolutionary tool, statistical coupling analysis. The results suggested that 5-hydroxytryptamine receptors and dopamine receptors have common conserved and coevolved residues. The Gα protein also have conserved and coevolved residues. These coevolved residues were implicated in the molecular functions of the analyzed proteins. We also found specific coevolving pairs related to the selectivity between GPCR and G protein were identified. We propose that these results would contribute to better understandings of not only the functional residues of GPCRs and Gα proteins but also GPCR-G protein selectivity mechanisms. Nature Publishing Group UK 2021-04-12 /pmc/articles/PMC8041822/ /pubmed/33846507 http://dx.doi.org/10.1038/s41598-021-87251-6 Text en © The Author(s) 2021 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Seo, Min Jae Heo, Joongyu Kim, Kyunghui Chung, Ka Young Yu, Wookyung Coevolution underlies GPCR-G protein selectivity and functionality |
title | Coevolution underlies GPCR-G protein selectivity and functionality |
title_full | Coevolution underlies GPCR-G protein selectivity and functionality |
title_fullStr | Coevolution underlies GPCR-G protein selectivity and functionality |
title_full_unstemmed | Coevolution underlies GPCR-G protein selectivity and functionality |
title_short | Coevolution underlies GPCR-G protein selectivity and functionality |
title_sort | coevolution underlies gpcr-g protein selectivity and functionality |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041822/ https://www.ncbi.nlm.nih.gov/pubmed/33846507 http://dx.doi.org/10.1038/s41598-021-87251-6 |
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