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Lifting the lid on GPCRs: the role of extracellular loops
M Wheatley1, D Wootten1, M T Conner1
1School of Biosciences, University of Birmingham, Birmingham, UKDrug Discovery Biology Laboratory, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, AustraliaDepartment of Pharmacology, Monash University, Parkville, Victoria, AustraliaSchool of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, UK.
Abstract:
GPCRs exhibit a common architecture of seven transmembrane helices (TMs) linked by intracellular loops and extracellular loops (ECLs). Given their peripheral location to the site of G-protein interaction, it might be assumed that ECL segments merely link the important TMs within the helical bundle of the receptor. However, compelling evidence has emerged in recent years revealing a critical role for ECLs in many fundamental aspects of GPCR function, which supported by recent GPCR crystal structures has provided mechanistic insights. This review will present current understanding of the key roles of ECLs in ligand binding, activation and regulation of both family A and family B GPCRs.
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