1rke
From Proteopedia
(New page: 200px<br /> <applet load="1rke" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rke, resolution 2.35Å" /> '''Human vinculin head...) |
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| - | [[Image:1rke.gif|left|200px]]<br /> | + | [[Image:1rke.gif|left|200px]]<br /><applet load="1rke" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1rke" size=" | + | |
caption="1rke, resolution 2.35Å" /> | caption="1rke, resolution 2.35Å" /> | ||
'''Human vinculin head (1-258) in complex with human vinculin tail (879-1066)'''<br /> | '''Human vinculin head (1-258) in complex with human vinculin tail (879-1066)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Vinculin is a conserved component and an essential regulator of both | + | Vinculin is a conserved component and an essential regulator of both cell-cell (cadherin-mediated) and cell-matrix (integrin-talin-mediated focal adhesions) junctions, and it anchors these adhesion complexes to the actin cytoskeleton by binding to talin in integrin complexes or to alpha-actinin in cadherin junctions. In its resting state, vinculin is held in a closed conformation through interactions between its head (Vh) and tail (Vt) domains. The binding of vinculin to focal adhesions requires its association with talin. Here we report the crystal structures of human vinculin in its inactive and talin-activated states. Talin binding induces marked conformational changes in Vh, creating a novel helical bundle structure, and this alteration actively displaces Vt from Vh. These results, as well as the ability of alpha-actinin to also bind to Vh and displace Vt from pre-existing Vh-Vt complexes, support a model whereby Vh functions as a domain that undergoes marked structural changes that allow vinculin to direct cytoskeletal assembly in focal adhesions and adherens junctions. Notably, talin's effects on Vh structure establish helical bundle conversion as a signalling mechanism by which proteins direct cellular responses. |
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| + | ==Disease== | ||
| + | Known disease associated with this structure: Cardiomyopathy, dilated, 1W OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=193065 193065]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 1RKE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1RKE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=1RKE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Bois, P | + | [[Category: Bois, P R.]] |
| - | [[Category: Borgon, R | + | [[Category: Borgon, R A.]] |
[[Category: Bricogne, G.]] | [[Category: Bricogne, G.]] | ||
[[Category: Evans, G.]] | [[Category: Evans, G.]] | ||
[[Category: Izard, T.]] | [[Category: Izard, T.]] | ||
| - | [[Category: Rush, C | + | [[Category: Rush, C L.]] |
[[Category: cytoskeleton; actin-binding; x-ray crystallography]] | [[Category: cytoskeleton; actin-binding; x-ray crystallography]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:51:51 2008'' |
Revision as of 12:51, 21 February 2008
|
Human vinculin head (1-258) in complex with human vinculin tail (879-1066)
Contents |
Overview
Vinculin is a conserved component and an essential regulator of both cell-cell (cadherin-mediated) and cell-matrix (integrin-talin-mediated focal adhesions) junctions, and it anchors these adhesion complexes to the actin cytoskeleton by binding to talin in integrin complexes or to alpha-actinin in cadherin junctions. In its resting state, vinculin is held in a closed conformation through interactions between its head (Vh) and tail (Vt) domains. The binding of vinculin to focal adhesions requires its association with talin. Here we report the crystal structures of human vinculin in its inactive and talin-activated states. Talin binding induces marked conformational changes in Vh, creating a novel helical bundle structure, and this alteration actively displaces Vt from Vh. These results, as well as the ability of alpha-actinin to also bind to Vh and displace Vt from pre-existing Vh-Vt complexes, support a model whereby Vh functions as a domain that undergoes marked structural changes that allow vinculin to direct cytoskeletal assembly in focal adhesions and adherens junctions. Notably, talin's effects on Vh structure establish helical bundle conversion as a signalling mechanism by which proteins direct cellular responses.
Disease
Known disease associated with this structure: Cardiomyopathy, dilated, 1W OMIM:[193065]
About this Structure
1RKE is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Vinculin activation by talin through helical bundle conversion., Izard T, Evans G, Borgon RA, Rush CL, Bricogne G, Bois PR, Nature. 2004 Jan 8;427(6970):171-5. Epub 2003 Dec 31. PMID:14702644
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