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| - | [[Image:Tr.png|left|200px|thumb|Crystal structure of human full-length Vinculin, [[1tr2]]]]
| + | <StructureSection load='1st6' size='340' side='right' caption='Chicken full-length metavinculin, [[1st6]]' scene='' > |
| - | {{STRUCTURE_1tr2| PDB=1tr2 | SIZE=300| SCENE=Vinculin/Cv/2 |right|CAPTION=Human full-length Vinculin, [[1tr2]] }}
| + | == Function == |
| | + | [[Vinculin|Vinculins]] (VCLs) are involved in adhesion by linking integrin molecules to the actin cytoskeleton. Its head domain (Vd1) can bind to [[Talin|talin]] or to [[Actinin|alpha-actinin]] at their respective VCL Binding Sites (VBS)<ref>PMID:11152287</ref>. The protein raver1 RNA Recognition Motif (RRM) forms a complex with VCL or m-VCL. '''Metavinculin''' (m-VCL) is a splice version of VCL containing an extra ca. 70 amino acids in the C-terminal domain. |
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| - | [[Vinculin|Vinculins]] (VCLs) are involved in adhesion by linking integrin molecules to the actin cytoskeleton. Its head domain (Vd1) can bind to [[Talin|talin]] or to [[Actinin|alpha-actinin]] at their respective VCL Binding Sites (VBS). A splice variant of vinculin is meta-vinculin (m-VCL). The protein raver1 RNA Recognition Motif (RRM) forms a complex with VCL or m-VCL. The images at the left and at the right correspond to one representative Vinculin structure, ''i.e.'' crystal structure of human full-length Vinculin ([[1tr2]]).
| + | == Relevance == |
| | + | Loss of VCL could be used as a prognostic factor for colorectal cancer se it promotes metastasis<ref>PMID:25496021</ref>. |
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| | + | == Disease == |
| | + | Mutation in m-VCL can yield cardiomyopathic phenotype<ref>PMID:16236538</ref>. |
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| | + | == Structural highlights == |
| | + | <scene name='Sandbox_27/Role_i997_vinculin_head-tail_1/1'>Vinculin Autoinhibition</scene> is achieved through a high affinity intramolecular interaction between tail (orange) and head (aqua) domains ([[1st6]]). Energetically, I997 is key to maintaining this autoinhibition. |
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| | == 3D Structures of Vinculin == | | == 3D Structures of Vinculin == |
| | + | [[Vinculin 3D structures]] |
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| + | ==References== |
| - | [[3myi]] – m-VCL tail domain – human<br />
| + | <references /> |
| - | [[3h2u]] – hVCL Vd1 + raver1 RRM<br />
| + | </StructureSection> |
| - | [[3h2v]] - hVCL C-terminal + raver1 RRM<br />
| + | |
| - | [[2ibf]], [[2hsq]], [[2gww]] - hVCL Vd1 + SfVCL binding sites from ''Shigella flexneri''<br />
| + | |
| - | [[2gdc]] – cm-VCL Vd1+SfInvasin C-terminal – chicken<br />
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| - | [[1tr2]] – hVCL<br />
| + | |
| - | [[1xwj]] - cm-VCL Vd1+cTalin VBS3<br />
| + | |
| - | [[1zvz]], [[1zw2]], [[1zw3]], [[1u6h]] - cm-VCL Vd1+cTalin rod<br />
| + | |
| - | [[1ydi]] - hVCL Vd1+hActinin VBS<br />
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| - | [[1t01]] - cVCL Vd1+mTalin VBS – mouse<br />
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| - | [[1st6]] – cm-VCL<br />
| + | |
| - | [[1syq]], [[1rkc]], [[1rke]] – hVCL Vd1+hTalin VBS<br />
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| - | [[1qkr]] – hVCL C-terminal<br />
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| | [[Category:Topic Page]] | | [[Category:Topic Page]] |
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| | + | *Created with the participation of [[User:Susan Craig|Susan Craig]]. |
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Function
Vinculins (VCLs) are involved in adhesion by linking integrin molecules to the actin cytoskeleton. Its head domain (Vd1) can bind to talin or to alpha-actinin at their respective VCL Binding Sites (VBS)[1]. The protein raver1 RNA Recognition Motif (RRM) forms a complex with VCL or m-VCL. Metavinculin (m-VCL) is a splice version of VCL containing an extra ca. 70 amino acids in the C-terminal domain.
Relevance
Loss of VCL could be used as a prognostic factor for colorectal cancer se it promotes metastasis[2].
Disease
Mutation in m-VCL can yield cardiomyopathic phenotype[3].
Structural highlights
is achieved through a high affinity intramolecular interaction between tail (orange) and head (aqua) domains (1st6). Energetically, I997 is key to maintaining this autoinhibition.
3D Structures of Vinculin
Vinculin 3D structures
References
- ↑ Palovuori R, Eskelinen S. Role of vinculin in the maintenance of cell-cell contacts in kidney epithelial MDBK cells. Eur J Cell Biol. 2000 Dec;79(12):961-74. PMID:11152287 doi:http://dx.doi.org/10.1078/0171-9335-00120
- ↑ Li T, Guo H, Song Y, Zhao X, Shi Y, Lu Y, Hu S, Nie Y, Fan D, Wu K. Loss of vinculin and membrane-bound beta-catenin promotes metastasis and predicts poor prognosis in colorectal cancer. Mol Cancer. 2014 Dec 11;13:263. doi: 10.1186/1476-4598-13-263. PMID:25496021 doi:http://dx.doi.org/10.1186/1476-4598-13-263
- ↑ 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
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