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| | ==Human vinculin head domain Vh1 (residues 1-258) in complex with the talin vinculin binding site 50 (VBS50, residues 2078-2099)== | | ==Human vinculin head domain Vh1 (residues 1-258) in complex with the talin vinculin binding site 50 (VBS50, residues 2078-2099)== |
| - | <StructureSection load='4dj9' size='340' side='right' caption='[[4dj9]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='4dj9' size='340' side='right'caption='[[4dj9]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dj9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DJ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DJ9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dj9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DJ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DJ9 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1rkc|1rkc]], [[1syq|1syq]], [[3s90|3s90]], [[3tj5|3tj5]], [[3tj6|3tj6]], [[1rke|1rke]]</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dj9 OCA], [https://pdbe.org/4dj9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dj9 RCSB], [https://www.ebi.ac.uk/pdbsum/4dj9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dj9 ProSAT]</span></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]), TLN1, KIAA1027, TLN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4dj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dj9 OCA], [http://pdbe.org/4dj9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dj9 RCSB], [http://www.ebi.ac.uk/pdbsum/4dj9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dj9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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> | + | [[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 == |
| - | [[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> [[http://www.uniprot.org/uniprot/TLN1_HUMAN TLN1_HUMAN]] Probably involved in connections of major cytoskeletal structures to the plasma membrane. High molecular weight cytoskeletal protein concentrated at regions of cell-substratum contact and, in lymphocytes, at cell-cell contacts (By similarity). | + | [[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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bricogne, G]] | + | [[Category: Large Structures]] |
| - | [[Category: Izard, T]] | + | [[Category: Bricogne G]] |
| - | [[Category: Rangarajan, E S]] | + | [[Category: Izard T]] |
| - | [[Category: Vonrhein, C]] | + | [[Category: Rangarajan ES]] |
| - | [[Category: Yogesha, S D]] | + | [[Category: Vonrhein C]] |
| - | [[Category: Cell adhesion]]
| + | [[Category: Yogesha SD]] |
| - | [[Category: Cytoskeleton]]
| + | |
| - | [[Category: Cytosol]]
| + | |
| - | [[Category: F-actin]]
| + | |
| - | [[Category: Focal adhesion]]
| + | |
| - | [[Category: Four-helix bundle]]
| + | |
| - | [[Category: Protein-protein interaction]]
| + | |
| Structural highlights
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
The cytoskeletal protein talin activates integrin receptors by binding of its FERM domain to the cytoplasmic tail of beta-integrin. Talin also couples integrins to the actin cytoskeleton, largely by binding to and activating the cytoskeletal protein vinculin, which binds to F-actin through the agency of its five-helix bundle tail (Vt) domain. Talin activates vinculin by means of buried amphipathic alpha-helices coined vinculin binding sites (VBSs) that reside within numerous four- and five-helix bundle domains that comprise the central talin rod, which are released from their buried locales by means of mechanical tension on the integrin:talin complex. In turn, these VBSs bind to the N-terminal seven-helix bundle (Vh1) domain of vinculin, creating an entirely new helix bundle that severs its head-tail interactions. Interestingly, talin harbors a second integrin binding site coined IBS2 that consists of two five-helix bundle domains that also contain a VBS (VBS50). Here we report the crystal structure of VBS50 in complex with vinculin at 2.3 A resolution and show that intramolecular interactions of VBS50 within IBS2 are much more extensive versus its interactions with vinculin. Indeed, the IBS2-vinculin interaction only occurs at physiological temperature and the affinity of VBS50 for vinculin is about 30 times less than other VBSs. The data support a model where integrin binding destabilizes IBS2 to allow it to bind to vinculin.
Crystal structure of vinculin in complex with vinculin binding site 50 (VBS50), the integrin binding site 2 (IBS2) of talin.,Yogesha SD, Rangarajan ES, Vonrhein C, Bricogne G, Izard T Protein Sci. 2012 Feb 14. doi: 10.1002/pro.2041. PMID:22334306[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Yogesha SD, Rangarajan ES, Vonrhein C, Bricogne G, Izard T. Crystal structure of vinculin in complex with vinculin binding site 50 (VBS50), the integrin binding site 2 (IBS2) of talin. Protein Sci. 2012 Feb 14. doi: 10.1002/pro.2041. PMID:22334306 doi:10.1002/pro.2041
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