1tx4: Difference between revisions

Small G proteins of the Rho family, which includes Rho, Rac and Cdc42Hs, regulate phosphorylation pathways that control a range of biological, functions including cytoskeleton formation and cell proliferation. They, operate as molecular switches, cycling between the biologically active, GTP-bound form and the inactive GDP-bound state. Their rate of hydrolysis, of GTP to GDP by virtue of their intrinsic GTPase activity is slow, but, can be accelerated by up to 10(5)-fold through interaction with rhoGAP, a, GTPase-activating protein that stimulates Rho-family proteins. As such, rhoGAP plays a crucial role in regulating Rho-mediated signalling, pathways. Here we report the crystal structure of RhoA and rhoGAP, complexed with the transition-state analogue GDP.AlF4- at 1.65 A, resolution. There is a rotation of 20 degrees between the Rho and rhoGAP, proteins in this complex when compared with the ground-state complex, Cdc42Hs.GMPPNP/rhoGAP, in which Cdc42Hs is bound to the non-hydrolysable, GTP analogue GMPPNP. Consequently, in the transition state complex but not, in the ground state, the rhoGAP domain contributes a residue, Arg85(GAP), directly into the active site of the G protein. We propose that this, residue acts to stabilize the transition state of the GTPase reaction., RhoGAP also appears to function by stabilizing several regions of RhoA, that are important in signalling the hydrolysis of GTP.

1TX4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, ALF and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: TS. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TX4 OCA].  

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