Ligand screening system using fusion proteins of G protein-coupled receptors with G protein α subunits

G protein-coupled receptors (GPCRs) constitute one of the largest families of genes in the human genome, and are the largest targets for drug development. Although a large number of GPCR genes have recently been identified, ligands have not yet been identified for many of them. Various assay systems have been employed to identify ligands for orphan GPCRs, but there is still no simple and general method to screen for ligands of such GPCRs, particularly of Gi-coupled receptors. We have examined whether fusion proteins of GPCRs with G protein α subunit (Gα) could be utilized for ligand screening and showed that the fusion proteins provide an effective method for the purpose. This article focuses on the followings: (1) characterization of GPCR genes and GPCRs, (2) identification of ligands for orphan GPCRs, (3) characterization of GPCR-Gα fusion proteins, and (4) identification of ligands for orphan GPCRs using GPCR-Gα fusion proteins.