| First Author | Chen Z | Year | 2008 |
| Journal | Structure | Volume | 16 |
| Issue | 10 | Pages | 1532-43 |
| PubMed ID | 18940608 | Mgi Jnum | J:245340 |
| Mgi Id | MGI:5918176 | Doi | 10.1016/j.str.2008.07.009 |
| Citation | Chen Z, et al. (2008) Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF. Structure 16(10):1532-43 |
| abstractText | G12 class heterotrimeric G proteins stimulate RhoA activation by RGS-RhoGEFs. However, p115RhoGEF is a GTPase Activating Protein (GAP) toward Galpha13, whereas PDZRhoGEF is not. We have characterized the interaction between the PDZRhoGEF rgRGS domain (PRG-rgRGS) and the alpha subunit of G13 and have determined crystal structures of their complexes in both the inactive state bound to GDP and the active states bound to GDP*AlF (transition state) and GTPgammaS (Michaelis complex). PRG-rgRGS interacts extensively with the helical domain and the effector-binding sites on Galpha13 through contacts that are largely conserved in all three nucleotide-bound states, although PRG-rgRGS has highest affinity to the Michaelis complex. An acidic motif in the N terminus of PRG-rgRGS occupies the GAP binding site of Galpha13 and is flexible in the GDP*AlF complex but well ordered in the GTPgammaS complex. Replacement of key residues in this motif with their counterparts in p115RhoGEF confers GAP activity. |
