Coevolution underlies GPCR-G protein selectivity and functionality

Abstract 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 prop...

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Autores principales:	Min Jae Seo, Joongyu Heo, Kyunghui Kim, Ka Young Chung, Wookyung Yu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b3576d08ff334e5cb17b5d4b1b84169a
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spelling	oai:doaj.org-article:b3576d08ff334e5cb17b5d4b1b84169a2021-12-02T15:51:16ZCoevolution underlies GPCR-G protein selectivity and functionality10.1038/s41598-021-87251-62045-2322https://doaj.org/article/b3576d08ff334e5cb17b5d4b1b84169a2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87251-6https://doaj.org/toc/2045-2322Abstract 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.Min Jae SeoJoongyu HeoKyunghui KimKa Young ChungWookyung YuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Min Jae Seo Joongyu Heo Kyunghui Kim Ka Young Chung Wookyung Yu Coevolution underlies GPCR-G protein selectivity and functionality
description	Abstract 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	article
author	Min Jae Seo Joongyu Heo Kyunghui Kim Ka Young Chung Wookyung Yu
author_facet	Min Jae Seo Joongyu Heo Kyunghui Kim Ka Young Chung Wookyung Yu
author_sort	Min Jae Seo
title	Coevolution underlies GPCR-G protein selectivity and functionality
title_short	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_sort	coevolution underlies gpcr-g protein selectivity and functionality
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b3576d08ff334e5cb17b5d4b1b84169a
work_keys_str_mv	AT minjaeseo coevolutionunderliesgpcrgproteinselectivityandfunctionality AT joongyuheo coevolutionunderliesgpcrgproteinselectivityandfunctionality AT kyunghuikim coevolutionunderliesgpcrgproteinselectivityandfunctionality AT kayoungchung coevolutionunderliesgpcrgproteinselectivityandfunctionality AT wookyungyu coevolutionunderliesgpcrgproteinselectivityandfunctionality
_version_	1718385654118744064

Coevolution underlies GPCR-G protein selectivity and functionality

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