1r6e
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Solution structure of the catalytic domain of SopE2
OverviewOverview
SopE and SopE2 are delivered by the Salmonella type III secretion system, into eukaryotic cells to promote cell invasion. SopE and SopE2 are potent, guanine nucleotide exchange factors (GEFs) for Rho GTPases Cdc42 and Rac1, and constitute a novel class of Rho GEFs. Although the sequence of, SopE-like GEFs is not at all homologous to those of the Dbl homology, domain-containing eukaryotic GEFs, the mechanism of nucleotide release, seems to have significant similarities. We have determined the solution, structure of the catalytic domain (residues 69-240) of SopE2, showing that, SopE2(69-240) comprises two three-helix bundles (alpha1alpha4alpha5 and, alpha2alpha3alpha6) arranged in a Lambda shape. Compared to the crystal, structure of SopE(78-240) in complex with Cdc42, SopE2(69-240) exhibits a, less open Lambda shape due to movement of SopE(78-240) helices alpha2 and, alpha5 to accommodate binding to the Cdc42 switch regions. In an NMR, titration to investigate the SopE2(69-240)-Cdc42 interaction, the, SopE2(69-240) residues affected by binding Cdc42 were very similar to the, SopE(78-240) residues that contact Cdc42 in the SopE(78-240)-Cdc42, complex. Analysis of the backbone (15)N dynamics of SopE2(69-240) revealed, flexibility in residues that link the two three-helix bundles, including, the alpha3-alpha4 linker that incorporates a beta-hairpin and the, catalytic loop, and the alpha5-alpha6 loop, and flexibility in residues, involved in interaction with Cdc42. Together, these observations provide, experimental evidence of a previously proposed mechanism of GEF-mediated, nucleotide exchange based on the Rac1-Tiam1 complex structure, with, SopE/E2 flexibility, particularly in the interbundle loops, enabling, conformational rearrangements of the nucleotide binding region of Cdc42, through an induced fit type of binding. Such flexibility in SopE/E2 may, also facilitate interaction through adaptive binding with alternative, target proteins such as Rab5, allograft inflammatory factor 1, and, apolipoprotein A-1.
About this StructureAbout this Structure
1R6E is a Single protein structure of sequence from Salmonella typhimurium lt2. Full crystallographic information is available from OCA.
ReferenceReference
solution structure, backbone dynamics, and interaction with Cdc42 of Salmonella guanine nucleotide exchange factor SopE2., Williams C, Galyov EE, Bagby S, Biochemistry. 2004 Sep 28;43(38):11998-2008. PMID:15379540
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