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3tj5

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Revision as of 23:16, 5 August 2016

human vinculin head domain (Vh1, residues 1-258) in complex with the vinculin binding site of the surface cell antigen 4 (sca4-VBS-N; residues 412-434) from Rickettsia rickettsii

Structural highlights

3tj5 is a 2 chain structure with sequence from Human and Ricro. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3rf3, 2ibf, 2hsq, 2gww, 1rkc, 3s90, 3tj6
Gene:	VCL (HUMAN), RrIowa_0797, sca4 (RICRO)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[VINC_HUMAN] Defects in VCL are the cause of cardiomyopathy dilated type 1W (CMD1W) [MIM: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.^[1] ^[2] Defects in VCL are the cause of familial hypertrophic cardiomyopathy type 15 (CMH15) [MIM: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.^[3]

Function

[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.^[4]

Publication Abstract from PubMed

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.

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Olson TM, Illenberger S, Kishimoto NY, Huttelmaier S, Keating MT, Jockusch BM. Metavinculin mutations alter actin interaction in dilated cardiomyopathy. Circulation. 2002 Jan 29;105(4):431-7. PMID:11815424
↑ Vasile VC, Will ML, Ommen SR, Edwards WD, Olson TM, Ackerman MJ. Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy. Mol Genet Metab. 2006 Feb;87(2):169-74. Epub 2005 Oct 19. PMID:16236538 doi:S1096-7192(05)00258-1
↑ Vasile VC, Ommen SR, Edwards WD, Ackerman MJ. A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2006 Jul 7;345(3):998-1003. Epub 2006 May 4. PMID:16712796 doi:S0006-291X(06)00981-8
↑ Le Clainche C, Dwivedi SP, Didry D, Carlier MF. Vinculin is a dually regulated actin filament barbed end-capping and side-binding protein. J Biol Chem. 2010 Jul 23;285(30):23420-32. doi: 10.1074/jbc.M110.102830. Epub, 2010 May 18. PMID:20484056 doi:10.1074/jbc.M110.102830
↑ Park H, Lee JH, Cossart P, Gouin E, Izard T. The Rickettsia surface cell antigen 4 applies mimicry to bind to and activate vinculin. J Biol Chem. 2011 Aug 13. PMID:21841197 doi:10.1074/jbc.M111.263855

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3tj5"

@@ Line 1: / Line 1: @@
 ==human vinculin head domain (Vh1, residues 1-258) in complex with the vinculin binding site of the surface cell antigen 4 (sca4-VBS-N; residues 412-434) from Rickettsia rickettsii==
 <StructureSection load='3tj5' size='340' side='right' caption='[[3tj5]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3tj5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rickettsia_rickettsii Rickettsia rickettsii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJ5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3tj5]] 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=3TJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJ5 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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]], [[3tj6|3tj6]]</td></tr>
-<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 Homo sapiens]), RrIowa_0797, sca4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=783 Rickettsia rickettsii])</td></tr>
+<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, sca4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=452659 RICRO])</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=3tj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tj5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tj5 RCSB], [http://www.ebi.ac.uk/pdbsum/3tj5 PDBsum]</span></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=3tj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tj5 OCA], [http://pdbe.org/3tj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tj5 RCSB], [http://www.ebi.ac.uk/pdbsum/3tj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tj5 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3tj5" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 27: / Line 29: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
-[[Category: Rickettsia rickettsii]]
+[[Category: Ricro]]
 [[Category: Cossart, P]]
 [[Category: Gouin, E]]

3tj5

From Proteopedia

Revision as of 23:16, 5 August 2016

human vinculin head domain (Vh1, residues 1-258) in complex with the vinculin binding site of the surface cell antigen 4 (sca4-VBS-N; residues 412-434) from Rickettsia rickettsii

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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