3tj6

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==human vinculin head domain (Vh1, residues 1-258) in complex with the vinculin binding site of the surface cell antigen 4 (sca4-VBS-C; residues 812-835) from Rickettsia rickettsii==
==human vinculin head domain (Vh1, residues 1-258) in complex with the vinculin binding site of the surface cell antigen 4 (sca4-VBS-C; residues 812-835) from Rickettsia rickettsii==
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<StructureSection load='3tj6' size='340' side='right' caption='[[3tj6]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
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<StructureSection load='3tj6' size='340' side='right'caption='[[3tj6]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3tj6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Ricro Ricro]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJ6 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3tj6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rickettsia_rickettsii_str._Iowa Rickettsia rickettsii str. Iowa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TJ6 FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rf3|3rf3]], [[2ibf|2ibf]], [[2hsq|2hsq]], [[2gww|2gww]], [[1rkc|1rkc]], [[3s90|3s90]], [[3tj5|3tj5]]</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.76&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VCL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RrIowa_0797 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=452659 RICRO])</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=3tj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tj6 OCA], [https://pdbe.org/3tj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tj6 RCSB], [https://www.ebi.ac.uk/pdbsum/3tj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tj6 ProSAT]</span></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=3tj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tj6 OCA], [http://pdbe.org/3tj6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tj6 RCSB], [http://www.ebi.ac.uk/pdbsum/3tj6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tj6 ProSAT]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/VINC_HUMAN VINC_HUMAN]] Defects in VCL are the cause of cardiomyopathy dilated type 1W (CMD1W) [MIM:[http://omim.org/entry/611407 611407]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:11815424</ref> <ref>PMID:16236538</ref> Defects in VCL are the cause of familial hypertrophic cardiomyopathy type 15 (CMH15) [MIM:[http://omim.org/entry/613255 613255]]. It is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.<ref>PMID:16712796</ref>
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[https://www.uniprot.org/uniprot/VINC_HUMAN VINC_HUMAN] Defects in VCL are the cause of cardiomyopathy dilated type 1W (CMD1W) [MIM:[https://omim.org/entry/611407 611407]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:11815424</ref> <ref>PMID:16236538</ref> Defects in VCL are the cause of familial hypertrophic cardiomyopathy type 15 (CMH15) [MIM:[https://omim.org/entry/613255 613255]. It is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.<ref>PMID:16712796</ref>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/VINC_HUMAN VINC_HUMAN]] Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion.<ref>PMID:20484056</ref>
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[https://www.uniprot.org/uniprot/VINC_HUMAN VINC_HUMAN] Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion.<ref>PMID:20484056</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Pathogenic Rickettsiae species cause high morbidity and mortality, especially R. prowazekii the causative agent of typhus. Like many intracellular pathogens, Rickettsiae exploit the cytoskeleton to enter and spread within the host cell. Here we report that the cell surface antigen sca4 of Rickettsiae colocalizes with vinculin in cells at sites of focal adhesions, and that sca4 binds to and activates vinculin through two vinculin binding sites (VBSs) that are conserved across all Rickettsia. Remarkably, this occurs through molecular mimicry of the vinculn-talin interaction that is also seen with the IpaA invasin of the intracellular pathogen Shigella, where binding of these VBSs to the vinculin seven-helix bundle head domain (Vh1) displaces intramolecular interactions with the vinculin tail domain that normally clamp vinculin in an inactive state. Finally, the vinculin:sca4-VBS crystal structures reveal that vinculin adopts a new conformation when bound to the C-terminal VBS of sca4. Collectively, our data define the mechanism by which sca4 activates vinculin and interacts with the actin cytoskeleton and they suggest important roles for vinculin in Rickettsia pathogenesis.
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The Rickettsia surface cell antigen 4 applies mimicry to bind to and activate vinculin.,Park H, Lee JH, Cossart P, Gouin E, Izard T J Biol Chem. 2011 Aug 13. PMID:21841197<ref>PMID:21841197</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 3tj6" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Ricro]]
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[[Category: Large Structures]]
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[[Category: Cossart, P]]
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[[Category: Rickettsia rickettsii str. Iowa]]
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[[Category: Gouin, E]]
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[[Category: Cossart P]]
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[[Category: Izard, T]]
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[[Category: Gouin E]]
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[[Category: Lee, J H]]
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[[Category: Izard T]]
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[[Category: Park, H]]
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[[Category: Lee JH]]
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[[Category: Alpha-helix bundle domain]]
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[[Category: Park H]]
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[[Category: Cell adhesion]]
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[[Category: Cytoskeleton]]
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[[Category: Cytosol]]
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[[Category: Epidemic typhus]]
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[[Category: Focal adhesion]]
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[[Category: Protein binding-toxin complex]]
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[[Category: Protein-protein interaction]]
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[[Category: Sca4]]
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[[Category: Spotted fever]]
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Current revision

human vinculin head domain (Vh1, residues 1-258) in complex with the vinculin binding site of the surface cell antigen 4 (sca4-VBS-C; residues 812-835) from Rickettsia rickettsii

PDB ID 3tj6

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