G protein-coupled receptor dimers: functional consequences, disease states and drug targets.
With an ever-expanding need for reliable therapeutic agents that are highly effective and exhibit minimal deleterious side effects, a greater understanding of the mechanisms underlying G protein-coupled receptor (GPCR) regulation is fundamental. GPCRs comprise more than 30% of all therapeutic drug targets and it is likely that this will only increase as more orphan GPCRs are identified. The past decade has seen a dramatic shift in the prevailing concept of how GPCRs function, in particular the growing acceptance that GPCRs are capable of interacting with one another at a molecular level to form complexes, with significantly different pharmacological properties to their monomeric selves. While the ability of like-receptors to associate and form homodimers raises some interesting mechanistic issues, the possibility that unlike-receptors could heterodimerise in certain tissue types, producing a functionally unique signalling complex that binds specific ligands, provides an invaluable opportunity to refine and redefine pharmacological interventions with greater specificity and efficacy.
Dalrymple
Matthew B
MB
Laboratory for Molecular Endocrinology - GPCRs, Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Perth, WA 6009, Australia.
Pfleger
Kevin D G
KD
Eidne
Karin A
KA
D000494:Allosteric Regulation; D000818:Animals; D019281:Dimerization; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism*
D043562:Receptors, G-Protein-Coupled