Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Allosteric Modulation of GPCRs of Class A by Cholesterol

Version 1 : Received: 20 January 2021 / Approved: 21 January 2021 / Online: 21 January 2021 (09:10:59 CET)

A peer-reviewed article of this Preprint also exists.

Jakubík, J.; El-Fakahany, E.E. Allosteric Modulation of GPCRs of Class A by Cholesterol. Int. J. Mol. Sci. 2021, 22, 1953. Jakubík, J.; El-Fakahany, E.E. Allosteric Modulation of GPCRs of Class A by Cholesterol. Int. J. Mol. Sci. 2021, 22, 1953.

Journal reference: Int. J. Mol. Sci. 2021, 22, 1953
DOI: 10.3390/ijms22041953

Abstract

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. Also, 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.

Keywords

GPCRs; cholesterol; allosteric modulation

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