5wez

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<StructureSection load='5wez' size='340' side='right' caption='[[5wez]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
<StructureSection load='5wez' size='340' side='right' caption='[[5wez]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5wez]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WEZ FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5wez]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Eco27 Eco27]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WEZ FirstGlance]. <br>
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</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=5wez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wez OCA], [http://pdbe.org/5wez PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wez RCSB], [http://www.ebi.ac.uk/pdbsum/5wez PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wez ProSAT]</span></td></tr>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cesT, E2348C_3940 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=574521 ECO27]), tir, espE, E2348C_3941 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=574521 ECO27])</td></tr>
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<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=5wez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wez OCA], [http://pdbe.org/5wez PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wez RCSB], [http://www.ebi.ac.uk/pdbsum/5wez PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wez ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/CEST_ECO27 CEST_ECO27]] Chaperone for the type III secretion of Tir. Probably stabilizes the protein, prevents inappropriate protein-proteininteractions and aids in secretion. [[http://www.uniprot.org/uniprot/TIR_ECO27 TIR_ECO27]] Multifunctional protein that is required for efficient pedestal formation in host epithelial cells during infection. The extracellular region acts as a receptor for bacterial intimin, allowing the bacterium to attach tightly to the host-cell surface. Simultaneously, the intracellular region initiates a signaling cascade in the host cell, which leads to actin polymerization and formation of actin pedestals at the sites of bacterial adhesion. In strain E2348/69, acts mainly via the host adaptor proteins NCK1 and NCK2. Once clustered and phosphorylated at Tyr-474, Tir binds to NCK proteins, which in turn bind and activate host WASL/N-WASP, leading to actin polymerization. Can also trigger an inefficient, NCK-independent pedestal formation. This pathway involves phosphorylation of Tyr-454 and probably a putative host adaptor. Acts also via direct binding to the host cytoskeletal protein alpha-actinin in a NCK- and phosphotyrosine-independent manner. This interaction may stabilize the pedestal, but is not essential for its formation.<ref>PMID:10096089</ref> <ref>PMID:14757753</ref> <ref>PMID:14764108</ref> <ref>PMID:15813734</ref> <ref>PMID:17521329</ref> <ref>PMID:9390560</ref>
[[http://www.uniprot.org/uniprot/CEST_ECO27 CEST_ECO27]] Chaperone for the type III secretion of Tir. Probably stabilizes the protein, prevents inappropriate protein-proteininteractions and aids in secretion. [[http://www.uniprot.org/uniprot/TIR_ECO27 TIR_ECO27]] Multifunctional protein that is required for efficient pedestal formation in host epithelial cells during infection. The extracellular region acts as a receptor for bacterial intimin, allowing the bacterium to attach tightly to the host-cell surface. Simultaneously, the intracellular region initiates a signaling cascade in the host cell, which leads to actin polymerization and formation of actin pedestals at the sites of bacterial adhesion. In strain E2348/69, acts mainly via the host adaptor proteins NCK1 and NCK2. Once clustered and phosphorylated at Tyr-474, Tir binds to NCK proteins, which in turn bind and activate host WASL/N-WASP, leading to actin polymerization. Can also trigger an inefficient, NCK-independent pedestal formation. This pathway involves phosphorylation of Tyr-454 and probably a putative host adaptor. Acts also via direct binding to the host cytoskeletal protein alpha-actinin in a NCK- and phosphotyrosine-independent manner. This interaction may stabilize the pedestal, but is not essential for its formation.<ref>PMID:10096089</ref> <ref>PMID:14757753</ref> <ref>PMID:14764108</ref> <ref>PMID:15813734</ref> <ref>PMID:17521329</ref> <ref>PMID:9390560</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Enteropathogenic Escherichia coli (EPEC) use a needle-like injection apparatus known as the type III secretion system (T3SS) to deliver protein effectors into host cells. Effector translocation is highly stratified in EPEC with the translocated intimin receptor (Tir) being the first effector delivered into the host. CesT is a multi-cargo chaperone that is required for the secretion of Tir and at least 9 other effectors. However, the structural and mechanistic basis for differential effector recognition by CesT remains unclear. Here, we delineated the minimal CesT-binding region on Tir to residues 35-77 and determined the 2.74 A structure of CesT bound to an N-terminal fragment of Tir. Our structure revealed that the CesT-binding region in the N-terminus of Tir contains an additional conserved sequence, distinct from the known chaperone-binding beta-motif, that we termed the CesT-extension motif because it extends the beta-sheet core of CesT. This motif is also present in the C-terminus of Tir that we confirmed to be a unique second CesT-binding region. Point mutations that disrupt CesT-binding to the N- or C-terminus of Tir revealed that the newly identified carboxy-terminal CesT-binding region was required for efficient Tir translocation into HeLa cells and pedestal formation. Furthermore, the CesT-extension motif was identified in the N-terminal region of NleH1, NleH2, and EspZ, and mutations that disrupt this motif reduced translocation of these effectors, and in some cases, overall effector stability, thus validating the universality of this CesT-extension motif. The presence of two CesT-binding regions in Tir, along with the presence of the CesT-extension motif in other highly translocated effectors, may contribute to differential cargo recognition by CesT.
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Molecular basis for CesT recognition of type III secretion effectors in enteropathogenic Escherichia coli.,Little DJ, Coombes BK PLoS Pathog. 2018 Aug 17;14(8):e1007224. doi: 10.1371/journal.ppat.1007224. PMID:30118511<ref>PMID:30118511</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5wez" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Eco27]]
[[Category: Coombes, B K]]
[[Category: Coombes, B K]]
[[Category: Little, D J]]
[[Category: Little, D J]]

Revision as of 07:51, 29 August 2018

Structure of the Tir-CesT effector-chaperone complex

5wez, resolution 2.74Å

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