GPCR dimerisation
Evidence has been obtained to indicate that GPCRs interact with other GPCRs to form
either homo- or heterodimers. In the case of the receptors in families B and C, the
evidence is that the functional activity (phenotype) of the receptors is linked to these
forms but in the case of family A receptors this link is less clear. The functional unit of
both the mGluR1 and GABABreceptors in family C, for example, is a homodimer and
X-ray crystallographic studies on the glutamate receptor have indicated that the
dimer exists as a dynamic equilibrium between two conformations, one ‘open’ theEndogenous
agonistBiased
agonist ABiased
agonist BGi–protein
activationGi–protein
activationGs–protein
activationGs–protein
activationb–Arrestin
signallingb–Arrestin
signallingDimerisationInternalisationInternalisationFig. 17.8Biased agonism. Whereas a natural agonist can activate the receptor to express all of its behaviour
towards its cellular host, some agonists can stabilise active receptor conformations that trigger only some of
these behaviours. Thus biased agonist A activates primary G-protein signalling pathways, whereas biased
agonist B activates mainly G-protein-independentb-arrestin signalling and internalisation. (Reproduced from
Kenakin, T. (2007). Collateral efficacy in drug discovery: taking advantage of the good (allosteric) nature of 7TM
receptors.Trends in Pharmacological Sciences, 28 , 407–412, by permission of Elsevier Science.)694 Cell membrane receptors and cell signalling