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PMID: 21864311 Published · ppublish English Journal Article Review

Lifting the lid on GPCRs: the role of extracellular loops.

British journal of pharmacology ·Vol. 165 ·No. 6 ·2012-03-00 ·Pages 1688-1703

Wheatley M, Wootten D, Conner MT, Simms J, Kendrick R, Logan RT, Poyner DR, Barwell J

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.

MeSH Terms
Binding Sites Humans Ligands Protein Conformation Receptors, G-Protein-Coupled/chemistry,metabolism
Chemicals
Ligands Receptors, G-Protein-Coupled
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Wheatley M
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.
Wootten D
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.
Conner M T
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.
Simms J
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.
Kendrick R
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.
Logan R T
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.
Poyner D R
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.
Barwell J
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.
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
1476-5381
DOI
10.1111/j.1476-5381.2011.01629.x
Published
2012-03-00
Pages
1688-1703
Language
English
Region
England
NLM ID
7502536
PMCID
PMC3372823
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1476-5381.2011.01629.x PMC Full Text View journal details
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