title: Lifting the lid on GPCRs: the role of extracellular loops.
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.
authors.affiliation: School 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.
authors.forename: M
authors.initials: M
authors.lastname: Wheatley
authors.affiliation: School 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.
authors.forename: D
authors.initials: D
authors.lastname: Wootten
authors.affiliation: School 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.
authors.forename: M T
authors.initials: MT
authors.lastname: Conner
authors.affiliation: School 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.
authors.forename: J
authors.initials: J
authors.lastname: Simms
authors.affiliation: School 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.
authors.forename: R
authors.initials: R
authors.lastname: Kendrick
authors.affiliation: School 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.
authors.forename: R T
authors.initials: RT
authors.lastname: Logan
authors.affiliation: School 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.
authors.forename: D R
authors.initials: DR
authors.lastname: Poyner
authors.affiliation: School 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.
authors.forename: J
authors.initials: J
authors.lastname: Barwell
mesh_terms: D001665:Binding Sites; D006801:Humans; D008024:Ligands; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled