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Structural and Functional Implication of Natural Variants of Gαs
Heterotrimeric guanine nucleotide-binding proteins (G proteins) are among the most important cellular signaling components, especially G protein-coupled receptors (GPCRs). G proteins comprise three subunits, Gα, Gβ, and Gγ. Gα is the key subunit, and its structural state regulates the active status...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959179/ https://www.ncbi.nlm.nih.gov/pubmed/36835474 http://dx.doi.org/10.3390/ijms24044064 |
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author | Jeong, Yejin Chung, Ka Young |
author_facet | Jeong, Yejin Chung, Ka Young |
author_sort | Jeong, Yejin |
collection | PubMed |
description | Heterotrimeric guanine nucleotide-binding proteins (G proteins) are among the most important cellular signaling components, especially G protein-coupled receptors (GPCRs). G proteins comprise three subunits, Gα, Gβ, and Gγ. Gα is the key subunit, and its structural state regulates the active status of G proteins. Interaction of guanosine diphosphate (GDP) or guanosine triphosphate (GTP) with Gα switches G protein into basal or active states, respectively. Genetic alteration in Gα could be responsible for the development of various diseases due to its critical role in cell signaling. Specifically, loss-of-function mutations of Gαs are associated with parathyroid hormone-resistant syndrome such as inactivating parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) signaling disorders (iPPSDs), whereas gain-of-function mutations of Gαs are associated with McCune–Albright syndrome and tumor development. In the present study, we analyzed the structural and functional implications of natural variants of the Gαs subtype observed in iPPSDs. Although a few tested natural variants did not alter the structure and function of Gαs, others induced drastic conformational changes in Gαs, resulting in improper folding and aggregation of the proteins. Other natural variants induced only mild conformational changes but altered the GDP/GTP exchange kinetics. Therefore, the results shed light on the relationship between natural variants of Gα and iPPSDs. |
format | Online Article Text |
id | pubmed-9959179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99591792023-02-26 Structural and Functional Implication of Natural Variants of Gαs Jeong, Yejin Chung, Ka Young Int J Mol Sci Article Heterotrimeric guanine nucleotide-binding proteins (G proteins) are among the most important cellular signaling components, especially G protein-coupled receptors (GPCRs). G proteins comprise three subunits, Gα, Gβ, and Gγ. Gα is the key subunit, and its structural state regulates the active status of G proteins. Interaction of guanosine diphosphate (GDP) or guanosine triphosphate (GTP) with Gα switches G protein into basal or active states, respectively. Genetic alteration in Gα could be responsible for the development of various diseases due to its critical role in cell signaling. Specifically, loss-of-function mutations of Gαs are associated with parathyroid hormone-resistant syndrome such as inactivating parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) signaling disorders (iPPSDs), whereas gain-of-function mutations of Gαs are associated with McCune–Albright syndrome and tumor development. In the present study, we analyzed the structural and functional implications of natural variants of the Gαs subtype observed in iPPSDs. Although a few tested natural variants did not alter the structure and function of Gαs, others induced drastic conformational changes in Gαs, resulting in improper folding and aggregation of the proteins. Other natural variants induced only mild conformational changes but altered the GDP/GTP exchange kinetics. Therefore, the results shed light on the relationship between natural variants of Gα and iPPSDs. MDPI 2023-02-17 /pmc/articles/PMC9959179/ /pubmed/36835474 http://dx.doi.org/10.3390/ijms24044064 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jeong, Yejin Chung, Ka Young Structural and Functional Implication of Natural Variants of Gαs |
title | Structural and Functional Implication of Natural Variants of Gαs |
title_full | Structural and Functional Implication of Natural Variants of Gαs |
title_fullStr | Structural and Functional Implication of Natural Variants of Gαs |
title_full_unstemmed | Structural and Functional Implication of Natural Variants of Gαs |
title_short | Structural and Functional Implication of Natural Variants of Gαs |
title_sort | structural and functional implication of natural variants of gαs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959179/ https://www.ncbi.nlm.nih.gov/pubmed/36835474 http://dx.doi.org/10.3390/ijms24044064 |
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