ArticleProtein science : a publication of the Protein Society2009
The solution structure and dynamics of the DH-PH module of PDZRhoGEF in isolation and in complex with nucleotide-free RhoA.
Article in Protein science : a publication of the Protein Society, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- A structural study of the complex between neuroepithelial cell transforming gene 1 (Net1) and RhoA reveals a potential anticancer drug hot spot.The Journal of biological chemistry · 2018Article
- HDX-MS guided drug discovery: small molecules and biopharmaceuticals.Current opinion in structural biology · 2014Review
- Structural insights into the activation of the RhoA GTPase by the lymphoid blast crisis (Lbc) oncoprotein.The Journal of biological chemistry · 2014Article
- The dynamic duo: combining NMR and small angle scattering in structural biology.Protein science : a publication of the Protein Society · 2014Review
- A Salmonella typhimurium-translocated glycerophospholipid:cholesterol acyltransferase promotes virulence by binding to the RhoA protein switch regions.The Journal of biological chemistry · 2012Article
- Optimization and stabilization of Rho small GTPase proteins for solution NMR studies: The case of Rnd1.Small GTPases · 2011Article
- Insights into the molecular activation mechanism of the RhoA-specific guanine nucleotide exchange factor, PDZRhoGEF.The Journal of biological chemistry · 2011Article
- Signalling mechanisms of RhoGTPase regulation by the heterotrimeric G proteins G12 and G13.Journal of biochemistry · 2011Review
- Mechanistic insights into specificity, activity, and regulatory elements of the regulator of G-protein signaling (RGS)-containing Rho-specific guanine nucleotide exchange factors (GEFs) p115, PDZ-RhoGEF (PRG), and leukemia-associated RhoGEF (LARG).The Journal of biological chemistry · 2011Article
- A new approach to explore the impact of freeze-thaw cycling on protein structure: hydrogen/deuterium exchange mass spectrometry (HX-MS).Pharmaceutical research · 2011Article
- Modulation of a GEF switch: autoinhibition of the intrinsic guanine nucleotide exchange activity of p115-RhoGEF.Protein science : a publication of the Protein Society · 2011Article
- Activated RhoA binds to the pleckstrin homology (PH) domain of PDZ-RhoGEF, a potential site for autoregulation.The Journal of biological chemistry · 2010Article
- Structure and function of heterotrimeric G protein-regulated Rho guanine nucleotide exchange factors.Molecular pharmacology · 2010Review
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The DH-PH domain tandems of Dbl-homology guanine nucleotide exchange factors catalyze the exchange of GTP for GDP in Rho-family GTPases, and thus initiate a wide variety of cellular signaling cascades. Although several crystal structures of complexes of DH-PH tandems with cognate, nucleotide free Rho GTPases are known, they provide limited information about the dynamics of the complex and it is not clear how accurately they represent the structures in solution. We used a complementary combination of nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and hydrogen-deuterium exchange mass spectrometry (DXMS) to study the solution structure and dynamics of the DH-PH tandem of RhoA-specific exchange factor PDZRhoGEF, both in isolation and in complex with nucleotide free RhoA. We show that in solution the DH-PH tandem behaves as a rigid entity and that the mutual disposition of the DH and PH domains remains identical within experimental error to that seen in the crystal structure of the complex, thus validating the latter as an accurate model of the complex in vivo. We also show that the nucleotide-free RhoA exhibits elevated dynamics when in complex with DH-PH, a phenomenon not observed in the crystal structure, presumably due to the restraining effects of crystal contacts. The complex is readily and rapidly dissociated in the presence of both GDP and GTP nucleotides, with no evidence of intermediate ternary complexes.
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