Isu, U.H.; Badiee, S.A.; Khodadadi, E.; Moradi, M. Cholesterol in Class C GPCRs: Role, Relevance, and Localization. Membranes2023, 13, 301.
Isu, U.H.; Badiee, S.A.; Khodadadi, E.; Moradi, M. Cholesterol in Class C GPCRs: Role, Relevance, and Localization. Membranes 2023, 13, 301.
Isu, U.H.; Badiee, S.A.; Khodadadi, E.; Moradi, M. Cholesterol in Class C GPCRs: Role, Relevance, and Localization. Membranes2023, 13, 301.
Isu, U.H.; Badiee, S.A.; Khodadadi, E.; Moradi, M. Cholesterol in Class C GPCRs: Role, Relevance, and Localization. Membranes 2023, 13, 301.
Abstract
G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and reviews on how cholesterol modulates class A GPCRs, however, this area of study is yet to be explored for class C GPCRs, which are characterized by a large extracellular region and often form constitutive dimers. This review highlights specific sites of interaction, functions, and structural dynamics involved in the cholesterol recognition of the class C GPCRs. We summarize recent data from some typical family members to explain the effects of membrane cholesterol on the structural features and functions of Class C GPCRs and speculate on their corresponding therapeutic potential.
Keywords
G-protein-coupled-receptors; GPCRs; Membrane protein; Protein-lipid interactions; Cholesterol; Class C GPCRs
Subject
Biology and Life Sciences, Biophysics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
