1r6e

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(New page: 200px<br /><applet load="1r6e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r6e" /> '''Solution structure of the catalytic domain o...)
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[[Image:1r6e.jpg|left|200px]]<br /><applet load="1r6e" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1r6e" />
 
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'''Solution structure of the catalytic domain of SopE2'''<br />
 
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==Overview==
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==Solution structure of the catalytic domain of SopE2==
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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.
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<StructureSection load='1r6e' size='340' side='right'caption='[[1r6e]]' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1r6e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium_str._LT2 Salmonella enterica subsp. enterica serovar Typhimurium str. LT2]. 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 [https://proteopedia.org/fgij/fg.htm?mol=1R6E FirstGlance]. <br>
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1R6E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_typhimurium_lt2 Salmonella typhimurium lt2]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R6E OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1r6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r6e OCA], [https://pdbe.org/1r6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r6e RCSB], [https://www.ebi.ac.uk/pdbsum/1r6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r6e ProSAT]</span></td></tr>
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==Reference==
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</table>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15379540 15379540]
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== Function ==
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[[Category: Salmonella typhimurium lt2]]
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[https://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>
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[[Category: Single protein]]
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== Evolutionary Conservation ==
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[[Category: Bagby, S.]]
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[[Image:Consurf_key_small.gif|200px|right]]
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[[Category: Galyov, E.E.]]
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Check<jmol>
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[[Category: Williams, C.]]
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<jmolCheckbox>
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[[Category: guanine nucleotide exchange factor]]
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r6/1r6e_consurf.spt"</scriptWhenChecked>
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[[Category: invasion]]
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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[[Category: salmonella]]
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<text>to colour the structure by Evolutionary Conservation</text>
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[[Category: type iii secretion]]
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1r6e ConSurf].
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:18:23 2007''
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Salmonella enterica subsp. enterica serovar Typhimurium str. LT2]]
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[[Category: Bagby S]]
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[[Category: Galyov EE]]
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[[Category: Williams C]]

Current revision

Solution structure of the catalytic domain of SopE2

PDB ID 1r6e

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