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| | ==Crystal structure of the force-sensing device region of alpha N-catenin== | | ==Crystal structure of the force-sensing device region of alpha N-catenin== |
| - | <StructureSection load='5xfl' size='340' side='right' caption='[[5xfl]], [[Resolution|resolution]] 2.45Å' scene=''> | + | <StructureSection load='5xfl' size='340' side='right'caption='[[5xfl]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xfl]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XFL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xfl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XFL FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3w3q|3w3q]], [[3w3r|3w3r]]</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]] 2.45Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ctnna2, Catna2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5xfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xfl OCA], [https://pdbe.org/5xfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xfl RCSB], [https://www.ebi.ac.uk/pdbsum/5xfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xfl 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=5xfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xfl OCA], [http://pdbe.org/5xfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xfl RCSB], [http://www.ebi.ac.uk/pdbsum/5xfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xfl ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CTNA2_MOUSE CTNA2_MOUSE]] May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation.<ref>PMID:12089526</ref> <ref>PMID:12123610</ref> <ref>PMID:15034585</ref> | + | [https://www.uniprot.org/uniprot/CTNA2_MOUSE CTNA2_MOUSE] May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation.<ref>PMID:12089526</ref> <ref>PMID:12123610</ref> <ref>PMID:15034585</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Mechanotransduction by alpha-catenin facilitates the force-dependent development of adherens junctions (AJs) by recruiting vinculin to reinforce actin anchoring of AJs. The alpha-catenin mechanotransducing action is facilitated by its force-sensing device region that autoinhibits the vinculin-binding site 1 (VBS1). Here, we report the high-resolution structure of the force-sensing device region of alpha-catenin, which shows the autoinhibited form comprised of helix bundles E, F and G. The cryptic VBS1 is embedded into helix bundle E stabilized by direct interactions with the autoinhibitory region forming helix bundles F and G. Our molecular dissection study showed that helix bundles F and G are stable in solution in each isolated form, whereas helix bundle E that contains VBS1 is unstable and intrinsically disordered in solution in the isolated form. We successfully identified key residues mediating the autoinhibition and produced mutated alpha-catenins that display variable force sensitivity and autoinhibition. Using these mutants, we demonstrate both in vitro and in vivo that, in the absence of this stabilization, the helix bundle containing VBS1 would adopt an unfolded form, thus exposing VBS for vinculin binding. We provide evidence for importance of mechanotransduction with the intrinsic force sensitivity for vinculin recruitment to adherens junctions of epithelial cell sheets with mutated alpha-catenins.
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| - | The force-sensing device region of alpha-catenin is an intrinsically disordered segment in the absence of intramolecular stabilization of the autoinhibitory form.,Hirano Y, Amano Y, Yonemura S, Hakoshima T Genes Cells. 2018 Mar 15. doi: 10.1111/gtc.12578. PMID:29542234<ref>PMID:29542234</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5xfl" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
| - | *[[Catenin|Catenin]] | + | *[[Catenin 3D structures|Catenin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Hakoshima, T]] | + | [[Category: Mus musculus]] |
| - | [[Category: Hirano, Y]] | + | [[Category: Hakoshima T]] |
| - | [[Category: Cell adhesion]] | + | [[Category: Hirano Y]] |
| - | [[Category: Cytoskeleton]]
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| - | [[Category: Mechanotransduction]]
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