| First Author | Nance MR | Year | 2013 |
| Journal | Structure | Volume | 21 |
| Issue | 3 | Pages | 438-48 |
| PubMed ID | 23434405 | Mgi Jnum | J:245268 |
| Mgi Id | MGI:5915358 | Doi | 10.1016/j.str.2012.12.016 |
| Citation | Nance MR, et al. (2013) Structural and functional analysis of the regulator of G protein signaling 2-galphaq complex. Structure 21(3):438-48 |
| abstractText | The heterotrimeric G protein Galphaq is a key regulator of blood pressure, and excess Galphaq signaling leads to hypertension. A specific inhibitor of Galphaq is the GTPase activating protein (GAP) known as regulator of G protein signaling 2 (RGS2). The molecular basis for how Galphaq/11 subunits serve as substrates for RGS proteins and how RGS2 mandates its selectivity for Galphaq is poorly understood. In crystal structures of the RGS2-Galphaq complex, RGS2 docks to Galphaq in a different orientation from that observed in RGS-Galphai/o complexes. Despite its unique pose, RGS2 maintains canonical interactions with the switch regions of Galphaq in part because its alpha6 helix adopts a distinct conformation. We show that RGS2 forms extensive interactions with the alpha-helical domain of Galphaq that contribute to binding affinity and GAP potency. RGS subfamilies that do not serve as GAPs for Galphaq are unlikely to form analogous stabilizing interactions. |
