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 alpha 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.
Milligan
Graeme
G
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK. g.milligan@bio.gla.ac.uk
Parenty
Geraldine
G
Stoddart
Leigh A
LA
Lane
J Robert
JR
D019281:Dimerization; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism*
D044385:GTP-Binding Protein alpha Subunits; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins