Related Experiment Video
Updated: Nov 15, 2025

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Allosteric Modulation of GPCRs of Class A by Cholesterol
Jan Jakubík1, Esam E El-Fakahany2
1Department of Neurochemistry, Institute of Physiology Czech Academy of Sciences, 142 20 Prague, Czech Republic.
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. 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.
Related Concept Videos
GPCRs Regulate Adenylyl Cylase Activity
G-Protein Gated Ion Channels
Sensory...
Allosteric Regulation
Cholinergic Receptors: Muscarinic
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....
GPCR Desensitization
Transducer Mechanism: G Protein–Coupled Receptors
GPCRs are also called heptahelical,...

