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| | ==Crystal structure of human 14-3-3 sigma in complex with a Tau-protein peptide surrounding pS324== | | ==Crystal structure of human 14-3-3 sigma in complex with a Tau-protein peptide surrounding pS324== |
| - | <StructureSection load='5btv' size='340' side='right' caption='[[5btv]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='5btv' size='340' side='right'caption='[[5btv]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5btv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BTV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BTV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5btv]] 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=5BTV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BTV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 1.7Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fl5|4fl5]]</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=5btv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5btv OCA], [https://pdbe.org/5btv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5btv RCSB], [https://www.ebi.ac.uk/pdbsum/5btv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5btv 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=5btv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5btv OCA], [http://pdbe.org/5btv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5btv RCSB], [http://www.ebi.ac.uk/pdbsum/5btv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5btv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. | + | [https://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5btv" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5btv" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Tau protein 3D structures|Tau protein 3D structures]] |
| | + | *[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bartel, M]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Ottmann, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Schumacher, B]] | + | [[Category: Bartel M]] |
| - | [[Category: 14-3-3]] | + | [[Category: Ottmann C]] |
| - | [[Category: Peptide binding protein]] | + | [[Category: Schumacher B]] |
| - | [[Category: Structural protein]]
| + | |
| - | [[Category: Tau-protein]]
| + | |
| Structural highlights
5btv is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.7Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
1433S_HUMAN Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.
Publication Abstract from PubMed
14-3-3 proteins act as adapters that exert their function by interacting with their various protein partners. 14-3-3 proteins have been implicated in a variety of human diseases including neurodegenerative diseases. 14-3-3 proteins have recently been reported to be abundant in the neurofibrillary tangles (NFTs) observed inside the neurons of brains affected by Alzheimer's disease (AD). These NFTs are mainly constituted of phosphorylated Tau protein, a microtubule-associated protein known to bind 14-3-3. Despite this indication of 14-3-3 protein involvement in the AD pathogenesis, the role of 14-3-3 in the Tauopathy remains to be clarified. In the present study, we shed light on the role of 14-3-3 proteins in the molecular pathways leading to Tauopathies. Overexpression of the 14-3-3sigma isoform resulted in a disruption of the tubulin cytoskeleton and prevented neuritic outgrowth in neurons. NMR studies validated the phosphorylated residues pSer214 and pSer324 in Tau as the 2 primary sites for 14-3-3 binding, with the crystal structure of 14-3-3sigma in complex with Tau-pSer214 and Tau-pSer324 revealing the molecular details of the interaction. These data suggest a rationale for a possible pharmacologic intervention of the Tau/14-3-3 interaction.
Involvement of 14-3-3 in tubulin instability and impaired axon development is mediated by Tau.,Joo Y, Schumacher B, Landrieu I, Bartel M, Smet-Nocca C, Jang A, Choi HS, Jeon NL, Chang KA, Kim HS, Ottmann C, Suh YH FASEB J. 2015 Oct;29(10):4133-44. doi: 10.1096/fj.14-265009. Epub 2015 Jun 23. PMID:26103986[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Joo Y, Schumacher B, Landrieu I, Bartel M, Smet-Nocca C, Jang A, Choi HS, Jeon NL, Chang KA, Kim HS, Ottmann C, Suh YH. Involvement of 14-3-3 in tubulin instability and impaired axon development is mediated by Tau. FASEB J. 2015 Oct;29(10):4133-44. doi: 10.1096/fj.14-265009. Epub 2015 Jun 23. PMID:26103986 doi:http://dx.doi.org/10.1096/fj.14-265009
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