Novel pharmacological applications of G-protein-coupled receptor–G protein fusions

Single, bi-functional polypeptides consisting of a G-protein-coupled receptor (GPCR) linked directly to a G protein α subunit have been employed for a number of years to study many aspects of signal initiation, including the roles of post-translational modifications, effects of mutations in both receptor and G protein and in the de-orphanisation of novel G-protein-coupled receptors. Recently, they have been used to improve signal-to-background in ligand assay screens and to study both agonist-directed signal trafficking and distinct conformational states of receptors. As well as such novel concepts in pharmacology, G-protein-coupled receptor–G protein fusions have recently been employed to examine receptor homo-dimerisation and hetero-dimerisation and are beginning to be used to explore allosteric effects within GPCR hetero-dimers.