Lifting the lid on GPCRs: the role of extracellular loops

Mark Wheatley, Denise Laura Wootten, Matthew Conner, John Watson Simms, R Kendrick, Ryan T Logan, David R Poyner, James Barwell

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235 Citations (Scopus)


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. LINKED ARTICLES This article is part of a themed section on the Molecular Pharmacology of G Protein-Coupled Receptors (GPCRs).
Original languageEnglish
Pages (from-to)1688 - 1703
Number of pages16
JournalBritish Journal of Pharmacology
Issue number6
Publication statusPublished - 2012

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