Allosteric modulation of GPCRs of class a by cholesterol

Jan Jakubík, Esam E. El-Fakahany

Research output: Contribution to journalReview articlepeer-review

36 Scopus citations


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.

Original languageEnglish (US)
Article number1953
Pages (from-to)1-18
Number of pages18
JournalInternational journal of molecular sciences
Issue number4
StatePublished - Feb 2 2021

Bibliographical note

Funding Information:
Funding: This research was funded by the Czech Academy of Sciences institutional support [RVO:67985823] and Grant Agency of the Czech Republic grant [19-05318S].

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Allosteric modulation
  • Cholesterol
  • GPCRs


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