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...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-02, Vol.22 (4), p.1953
Main Authors: Jakubík, Jan, El-Fakahany, Esam E
Format: Article
Language:English
Subjects:
Adenosine
allosteric modulation
Allosteric properties
Allosteric Regulation
Animals
Anticholesteremic Agents - pharmacology
Anticholesteremic Agents - therapeutic use
Binding sites
Binding Sites - drug effects
Cell Membrane - metabolism
Cholesterol
Cholesterol - chemistry
Cholesterol - metabolism
GPCRs
Humans
Ligands
Lipids
Localization
Membrane proteins
Membranes
Molecular Targeted Therapy - methods
Narcotics
Oligomerization
Protein Binding
Proteins
Receptors, G-Protein-Coupled - chemistry
Receptors, G-Protein-Coupled - classification
Receptors, G-Protein-Coupled - metabolism
Review
Reviews
Signal transduction
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22041953