| First Author | Masuho I | Year | 2020 |
| Journal | Cell | Volume | 183 |
| Issue | 2 | Pages | 503-521.e19 |
| PubMed ID | 33007266 | Mgi Jnum | J:298359 |
| Mgi Id | MGI:6477696 | Doi | 10.1016/j.cell.2020.08.052 |
| Citation | Masuho I, et al. (2020) A Global Map of G Protein Signaling Regulation by RGS Proteins. Cell 183(2):503-521.e19 |
| abstractText | The control over the extent and timing of G protein signaling is provided by the regulator of G protein signaling (RGS) proteins that deactivate G protein alpha subunits (Galpha). Mammalian genomes encode 20 canonical RGS and 16 Galpha genes with key roles in physiology and disease. To understand the principles governing the selectivity of Galpha regulation by RGS, we examine the catalytic activity of all canonical human RGS proteins and their selectivity for a complete set of Galpha substrates using real-time kinetic measurements in living cells. The data reveal rules governing RGS-Galpha recognition, the structural basis of its selectivity, and provide principles for engineering RGS proteins with defined selectivity. The study also explores the evolution of RGS-Galpha selectivity through ancestral reconstruction and demonstrates how naturally occurring non-synonymous variants in RGS alter signaling. These results provide a blueprint for decoding signaling selectivity and advance our understanding of molecular recognition principles. |
