Document Type
Article
Publication Title
Structure (London, England : 1993)
Publication Date
10-8-2008
Volume
16
Issue
10
Disciplines
Biology | Life Sciences
Abstract
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.
DOI
10.1016/j.str.2008.07.009
Rights
© 2008 Elsevier, Ltd.
Recommended Citation
Chen, Zhe; Singer, William D.; Danesh, Shahab M.; Sternweis, Paul C.; and Sprang, Stephen R., "Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF" (2008). Biological Sciences Faculty Publications. 502.
https://scholarworks.umt.edu/biosci_pubs/502