3cx8
From Proteopedia
Crystal Structure of PDZRhoGEF rgRGS Domain in a Complex with Galpha-13 Bound to GTP-gamma-S
Structural highlights
FunctionGNA13_MOUSE Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedG12 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. Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF.,Chen Z, Singer WD, Danesh SM, Sternweis PC, Sprang SR Structure. 2008 Oct 8;16(10):1532-43. PMID:18940608[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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