|
|
| (2 intermediate revisions by the same user not shown) |
| Line 1: |
Line 1: |
| | |
| ==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/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 [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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</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]), TLN1, KIAA1027, TLN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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='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://www.rcsb.org/pdb/explore.do?structureId=4dj9 RCSB], [http://www.ebi.ac.uk/pdbsum/4dj9 PDBsum]</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;">
| |
| == 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<ref>PMID:22334306</ref>
| |
| | |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| |
| </div>
| |
|
| |
|
| ==See Also== | | ==See Also== |
| *[[Talin|Talin]] | | *[[Talin 3D structures|Talin 3D structures]] |
| *[[Vinculin|Vinculin]] | | *[[Vinculin|Vinculin]] |
| == References == | | == References == |
| Line 28: |
Line 20: |
| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]] | | [[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]]
| |