N-terminal Dbl domain of the RhoGEF, Kalirin
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Guanine nucleotide exchange factors (GEF) promote the release of GDP from GTPases, thus allowing the free GTPase molecule to bind the more abundant GTP molecule. In the GTP-bound state, the GTPase elicits signal transduction by acting on its effector proteins. Spontaneous release of GDP is a slow process and the catalysis of the GDP release by a GEF is generally a prerequisite for efficient signaling (Vetter and Wittinghofer 2001). The structurally related GEFs form subfamilies that regulate a specific family of GTPase proteins. GEFs that activate Rho GTPases have been implicated in cancer and mental retardation. RhoGEFs are a relatively large family, and many of the ~69 human RhoGEFs were discovered based on their oncogenic activation in cancer and cancer models. The catalytic components of RhoGEFs are referred to as Dbl homology domains, after the screen that identified the protein Dbl encoded by the diffuse B-cell lymphoma (dbl) oncogene (Eva and Aaronson 1985)....
KeywordsRoot Mean Square Deviation Guanine Nucleotide Exchange Factor Residual Dipolar Coupling Final Ensemble Experimental Restraint
Support from the US National Institutes of Health is gratefully acknowledged (grants MH65567 to M.R.S., and RR020125 and GM047467 to J.C.H.). We thank Dr. Jeffrey Lary from the National Analytical Ultracentrifugation Facility, The University of Connecticut, Storrs, USA for performing the analytical ultracentrifugation experiments and Dr. Mark Maciejewski for helpful discussion and suggestions on NMR experiments. We thank Dr. Andrei Alexandrescu for the Pf1 phage and help with preliminary RDC experiments.
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