Insights into ligand pharmacology using receptor-G-protein fusion proteins

Production of chimeric DNAs in which the 5' end of G-protein alpha-subunits are linked directly to the 3' tail of a G-protein-coupled receptor has recently offered an unusual strategy to explore the detailed pharmacology of receptor-G-protein interactions. Expression of such fusion proteins ensures a 1:1 stoichiometry of receptor and G-protein expression and their proximity to each other. The capacity of such fusion proteins to be regarded as agonist-activated GTPases that allow simple enzyme kinetics to be applied to issues of ligand efficacy will be considered. In addition, the effects of point mutations, in both receptors and G proteins, on ligand function are particularly amenable to the types of robust quantitative analyses that can be produced using such fusion proteins.