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3rf3

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Revision as of 00:07, 5 August 2016

Shigella IpaA-VBS3 in complex with human vinculin

Structural highlights

3rf3 is a 4 chain structure with sequence from "shigella_paradysenteriae"_weldin_1927 "shigella paradysenteriae" weldin 1927 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2gww, 2hsq, 2ibf
Gene:	VCL, vinculin (HUMAN), CP0125, ipaA ("Shigella paradysenteriae" Weldin 1927)
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] [IPAA_SHIFL] Rapidly associates with the first 265 amino acids of vinculin after bacteria-cell contact. This interaction is critical for efficient Shigella uptake. IpaA acts as a potent activator of vinculin and increase its ability to interact with F-actin. The complex IpaA-vinculin induces F-actin depolymerization along with the occasional formation of actin filament bundles.^[5] ^[6]

Publication Abstract from PubMed

Internalization of Shigella into host epithelial cells, where the bacteria replicates and spreads to neighboring cells, requires a type 3 secretion system (T3SS) effector coined IpaA. IpaA binds directly to and activates the cytoskeletal protein vinculin after injection in the host cell cytosol, and this was previously thought to be directed by two amphipathic alpha-helical vinculin-binding sites (VBS) found in the C-terminal tail domain of IpaA. Here, we report a third VBS, IpaA-VBS3, that is located N-terminal to the other two VBSs of IpaA and show that one IpaA molecule can bind up to three vinculin molecules. Biochemical in vitro Shigella invasion assays and the 1.6 A crystal structure of the vinculin.IpaA-VBS3 complex showed that IpaA-VBS3 is functionally redundant with the other two IpaA-VBSs in cell invasion and in activating the latent F-actin binding functions of vinculin. Multiple VBSs in IpaA are reminiscent of talin, which harbors 11 VBSs. However, most of the talin VBSs have low affinity and are buried in helix bundles, whereas all three of the VBSs of IpaA are high affinity, readily available, and in close proximity to each other in the IpaA structure. Although deletion of IpaA-VBS3 has no detectable effects on Shigella invasion of epithelial cells, deletion of all three VBSs impaired bacterial invasion to levels found in an ipaA null mutant strain. Thus, IpaA-directed mimicry of talin in activating vinculin occurs through three high affinity VBSs that are essential for Shigella pathogenesis.

Novel vinculin binding site of the IpaA invasin of Shigella.,Park H, Valencia-Gallardo C, Sharff A, Tran Van Nhieu G, Izard T J Biol Chem. 2011 Jul 1;286(26):23214-21. Epub 2011 Apr 27. PMID:21525010^[7]

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
↑ Tran Van Nhieu G, Ben-Ze'ev A, Sansonetti PJ. Modulation of bacterial entry into epithelial cells by association between vinculin and the Shigella IpaA invasin. EMBO J. 1997 May 15;16(10):2717-29. PMID:9184218 doi:10.1093/emboj/16.10.2717
↑ Bourdet-Sicard R, Rudiger M, Jockusch BM, Gounon P, Sansonetti PJ, Nhieu GT. Binding of the Shigella protein IpaA to vinculin induces F-actin depolymerization. EMBO J. 1999 Nov 1;18(21):5853-62. PMID:10545097 doi:10.1093/emboj/18.21.5853
↑ Park H, Valencia-Gallardo C, Sharff A, Tran Van Nhieu G, Izard T. Novel vinculin binding site of the IpaA invasin of Shigella. J Biol Chem. 2011 Jul 1;286(26):23214-21. Epub 2011 Apr 27. PMID:21525010 doi:10.1074/jbc.M110.184283

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/3rf3"

@@ Line 1: / Line 1: @@
 ==Shigella IpaA-VBS3 in complex with human vinculin==
 <StructureSection load='3rf3' size='340' side='right' caption='[[3rf3]], [[Resolution|resolution]] 1.61&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rf3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Shigella_flexneri Shigella flexneri]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RF3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RF3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rf3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"shigella_paradysenteriae"_weldin_1927 "shigella paradysenteriae" weldin 1927] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RF3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RF3 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2gww|2gww]], [[2hsq|2hsq]], [[2ibf|2ibf]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VCL, vinculin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CP0125, ipaA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=623 Shigella flexneri])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VCL, vinculin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CP0125, ipaA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=623 "Shigella paradysenteriae" Weldin 1927])</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=3rf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rf3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rf3 RCSB], [http://www.ebi.ac.uk/pdbsum/3rf3 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=3rf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rf3 OCA], [http://pdbe.org/3rf3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rf3 RCSB], [http://www.ebi.ac.uk/pdbsum/3rf3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rf3 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 3rf3" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 27: / Line 29: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Shigella paradysenteriae weldin 1927]]
-[[Category: Shigella flexneri]]
+[[Category: Human]]
 [[Category: Izard, T]]
 [[Category: Park, H]]

3rf3

From Proteopedia

Revision as of 00:07, 5 August 2016

Shigella IpaA-VBS3 in complex with human vinculin

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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