Class A GPCR heterodimers: evidence from binding studies.
There is a large body of experimental evidence that is compatible with the presence of heterodimers of the major A subclass of G protein-coupled receptors (GPCRs) and suggests that these heterodimers might have different functional properties from those of the monomers (or homodimers) of the individual receptors that engage in heterodimer formation. The question is whether there are allosteric interactions across the receptor-receptor interface of a heterodimer that modulate the binding properties of the heterodimer components and thereby change their pharmacology. In this review, I examine published experimental evidence from radioligand binding studies in the context of different models of allosterism and discuss a number of apparently discrepant results. The analysis suggests that more experimental data are required if equal, two-way, crossreceptor interactions within a GPCR heterodimer, at the level of binding, are to be unequivocally demonstrated.
Birdsall
Nigel J M
NJ
Division of Physical Biochemistry, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK. nbirdsa@nimr.mrc.ac.uk
D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D055503:Protein Multimerization; D011869:Radioligand Assay; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry / Q000378:metabolism; D017983:Receptors, Catecholamine / Q000737:chemistry / Q000378:metabolism; D019707:Receptors, Chemokine / Q000737:chemistry / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000737:chemistry / Q000378:metabolism
D043884:Receptor, Cannabinoid, CB1; D017983:Receptors, Catecholamine; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D018094:Receptors, Metabotropic Glutamate; D018013:Receptors, Neuropeptide; C108822:metabotropic glutamate receptor 2; D019204:GTP-Binding Proteins