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Allosteric Modulation of GPCRs of Class A by Cholesterol
G-protein coupled receptors (GPCRs) are membrane proteins that convey extracellular signals to the cellular milieu. They represent a target for more than 30% of currently marketed drugs. Here we review the effects of membrane cholesterol on the function of GPCRs of Class A. We review both the specif...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920425/ https://www.ncbi.nlm.nih.gov/pubmed/33669406 http://dx.doi.org/10.3390/ijms22041953 |
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author | Jakubík, Jan El-Fakahany, Esam E. |
author_facet | Jakubík, Jan El-Fakahany, Esam E. |
author_sort | Jakubík, Jan |
collection | PubMed |
description | G-protein coupled receptors (GPCRs) are membrane proteins that convey extracellular signals to the cellular milieu. They represent a target for more than 30% of currently marketed drugs. Here we review the effects of membrane cholesterol on the function of GPCRs of Class A. We review both the specific effects of cholesterol mediated via its direct high-affinity binding to the receptor and non-specific effects mediated by cholesterol-induced changes in the properties of the membrane. Cholesterol binds to many GPCRs at both canonical and non-canonical binding sites. It allosterically affects ligand binding to and activation of GPCRs. Additionally, it changes the oligomerization state of GPCRs. In this review, we consider a perspective of the potential for the development of new therapies that are targeted at manipulating the level of membrane cholesterol or modulating cholesterol binding sites on to GPCRs. |
format | Online Article Text |
id | pubmed-7920425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79204252021-03-02 Allosteric Modulation of GPCRs of Class A by Cholesterol Jakubík, Jan El-Fakahany, Esam E. Int J Mol Sci Review G-protein coupled receptors (GPCRs) are membrane proteins that convey extracellular signals to the cellular milieu. They represent a target for more than 30% of currently marketed drugs. Here we review the effects of membrane cholesterol on the function of GPCRs of Class A. We review both the specific effects of cholesterol mediated via its direct high-affinity binding to the receptor and non-specific effects mediated by cholesterol-induced changes in the properties of the membrane. Cholesterol binds to many GPCRs at both canonical and non-canonical binding sites. It allosterically affects ligand binding to and activation of GPCRs. Additionally, it changes the oligomerization state of GPCRs. In this review, we consider a perspective of the potential for the development of new therapies that are targeted at manipulating the level of membrane cholesterol or modulating cholesterol binding sites on to GPCRs. MDPI 2021-02-16 /pmc/articles/PMC7920425/ /pubmed/33669406 http://dx.doi.org/10.3390/ijms22041953 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Jakubík, Jan El-Fakahany, Esam E. Allosteric Modulation of GPCRs of Class A by Cholesterol |
title | Allosteric Modulation of GPCRs of Class A by Cholesterol |
title_full | Allosteric Modulation of GPCRs of Class A by Cholesterol |
title_fullStr | Allosteric Modulation of GPCRs of Class A by Cholesterol |
title_full_unstemmed | Allosteric Modulation of GPCRs of Class A by Cholesterol |
title_short | Allosteric Modulation of GPCRs of Class A by Cholesterol |
title_sort | allosteric modulation of gpcrs of class a by cholesterol |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920425/ https://www.ncbi.nlm.nih.gov/pubmed/33669406 http://dx.doi.org/10.3390/ijms22041953 |
work_keys_str_mv | AT jakubikjan allostericmodulationofgpcrsofclassabycholesterol AT elfakahanyesame allostericmodulationofgpcrsofclassabycholesterol |