A high-throughput method capable of assaying a large fraction of all G protein-coupled receptors (GPCRs)-the target of many drug discovery efforts-is reported this week in Nature Methods. This assaying technique allows for analysis of GPCRs that have thus far been intractable with previous methods.
GPCRs are the largest family of cell-signaling proteins and, but existing assays have limitations, which has hindered some drug discover efforts.
Junken Aoki and colleagues developed a ‘shedding assay’ that first stimulates GPCR-expressing cells with ligands and then measures the response in the release of a protein from the surface the cells. The assay found activators for 90% of 116 GPCRs, including 14 that were previously uncharacterized. They further used the assay to identify the endogenous ligand for three orphan receptors whose biological ligand was previously unknown.
The shedding assay could be a valuable addition to the repertoire of high-throughput assays available to researchers trying to untangle the biology of this ubiquitous class of cell receptors, as well as those seeking to match GPCRs with the drugs that control their function.