1r6e

<StructureSection load='1r6e' size='340' side='right' caption='[[1r6e]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[1r6e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Salty Salty]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R6E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1R6E FirstGlance]. <br>

</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SopE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=99287 SALTY])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1r6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r6e OCA], [http://pdbe.org/1r6e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1r6e RCSB], [http://www.ebi.ac.uk/pdbsum/1r6e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1r6e ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/SOPE2_SALTY SOPE2_SALTY]] Activator for CDC42 by directly engaging this Rho GTPase and acting as potent guanine nucleotide exchange factor (GEF). This activation results in actin cytoskeleton rearrangements and stimulates membrane ruffling, promoting bacterial entry into non-phagocytic cells. Also activates NF-kB, p38 and ERK kinases, which are known to be involved in the induction of IL-8 expression. Chaperone InvB is required for secretion, translocation and stabilization of intracellular levels of sopE2.<ref>PMID:10931274</ref> <ref>PMID:15321998</ref>

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

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.

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<ref>PMID:15379540</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 1r6e" style="background-color:#fffaf0;"></div>

[[Category: Salty]]

[[Category: Bagby, S]]

[[Category: Galyov, E E]]

[[Category: Williams, C]]

[[Category: Cell invasion]]

[[Category: Type iii secretion]]