1cc0

From Proteopedia

Revision as of 13:35, 15 February 2008

CRYSTAL STRUCTURE OF THE RHOA.GDP-RHOGDI COMPLEX

Overview

Like all Rho (Ras homology) GTPases, RhoA functions as a molecular switch, in cell signaling, alternating between GTP- and GDP-bound states, with its, biologically inactive GDP-bound form maintained as a cytosolic complex, with RhoGDI (guanine nucleotide-exchange inhibitor). The crystal, structures of RhoA-GDP and of the C-terminal immunoglobulin-like domain of, RhoGDI (residues 67-203) are known, but the mechanism by which the two, proteins interact is not known. The functional human RhoA-RhoGDI complex, has been expressed in yeast and crystallized (P6(5)22, unit-cell, parameters a = b = 139, c = 253 A, two complexes in the asymmetric unit)., Although diffraction from these crystals extends to 3.5 A and is highly, anisotropic, the experimentally phased (MAD plus MIR) electron-density map, was adequate to reveal the mutual disposition of the two molecules. The, result was validated by molecular-replacement calculations when data were, corrected for anisotropy. Furthermore, the N-terminus of RhoGDI (the, region involved in inhibition of nucleotide exchange) can be identified in, the electron-density map: it is bound to the switch I and switch II, regions of RhoA, occluding an epitope which binds Dbl-like, nucleotide-exchange factors. The entrance of the hydrophobic pocket of, RhoGDI is 25 A from the last residue in the RhoA model, with its, C-terminus oriented to accommodate the geranylgeranyl group without, conformational change in RhoA.

About this Structure

1CC0 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

Reference

How RhoGDI binds Rho., Longenecker K, Read P, Derewenda U, Dauter Z, Liu X, Garrard S, Walker L, Somlyo AV, Nakamoto RK, Somlyo AP, Derewenda ZS, Acta Crystallogr D Biol Crystallogr. 1999 Sep;55(Pt 9):1503-15. PMID:10489445

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