GPCR-Gα fusion proteins:: molecular analysis of receptor-G-protein coupling

The efficiency of interactions between G-pratein-coupled receptors (GPCRs) and heterotrimeric guanine nucleotide-binding proteins (G proteins) is greatly influenced by the absolute and relative densities of these proteins in the plasma membrane. The study of these interactions has been facilitated by the use of GPCR-G alpha fusion proteins, which are formed by the fusion of GPCR to Ga. These fusion proteins ensure a defined 1:1 stoichiometry of GPCR to GOL and force the physical proximity of the signalling partners. Thus, fusion of GPCR to G alpha enhances coupling efficiency can be used to study aspects of receptor-G-protein coupling that could not otherwise be examined by co-expressing GPCRs and G proteins as separate proteins. The results of studies that have made use of GPCR-G alpha fusion proteins will be discussed in this article, along with the strengths and limitations of this approach.