title: Allostery in GPCRs: 'MWC' revisited.
abstract: G protein-coupled receptors (GPCRs) constitute the largest family of receptors in the genome and are the targets for at least 30% of current medicines. In recent years, there has been a dramatic increase in the discovery of allosteric modulators of GPCR activity and a growing appreciation of the diverse modes by which GPCRs can be regulated by both orthosteric and allosteric ligands. Interestingly, some of the contemporary views of GPCR function reflect characteristics that are shared by prototypical allosteric proteins, as encompassed in the classic Monod-Wyman-Changeux (MWC) model initially proposed for enzymes and subsequently extended to other protein families. In this review, we revisit the MWC model in the context of emerging structural, functional and operational data on GPCR allostery.
authors.affiliation: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Australia.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Canals
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sexton
authors.forename: Arthur
authors.initials: A
authors.lastname: Christopoulos
mesh_terms: D000495:Allosteric Site; D000818:Animals; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D009097:Multienzyme Complexes; D043562:Receptors, G-Protein-Coupled