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| | ==Crystal structure of human TLE1 Q-domain residues 20-156== | | ==Crystal structure of human TLE1 Q-domain residues 20-156== |
| - | <StructureSection load='4om3' size='340' side='right' caption='[[4om3]], [[Resolution|resolution]] 2.85Å' scene=''> | + | <StructureSection load='4om3' size='340' side='right'caption='[[4om3]], [[Resolution|resolution]] 2.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4om3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OM3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OM3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4om3]] is a 4 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=4OM3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OM3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.855Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4om2|4om2]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLE, TLE1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4om3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4om3 OCA], [https://pdbe.org/4om3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4om3 RCSB], [https://www.ebi.ac.uk/pdbsum/4om3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4om3 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=4om3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4om3 OCA], [http://pdbe.org/4om3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4om3 RCSB], [http://www.ebi.ac.uk/pdbsum/4om3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4om3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TLE1_HUMAN TLE1_HUMAN]] Transcriptional corepressor that binds to a number of transcription factors. Inhibits NF-kappa-B-regulated gene expression. Inhibits the transcriptional activation mediated by FOXA2, and by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Unusual function as coactivator for ESRRG.<ref>PMID:10660609</ref> | + | [https://www.uniprot.org/uniprot/TLE1_HUMAN TLE1_HUMAN] Transcriptional corepressor that binds to a number of transcription factors. Inhibits NF-kappa-B-regulated gene expression. Inhibits the transcriptional activation mediated by FOXA2, and by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Unusual function as coactivator for ESRRG.<ref>PMID:10660609</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Wnt signaling activates target genes by promoting association of the co-activator beta-catenin with TCF/LEF transcription factors. In the absence of beta-catenin, target genes are silenced by TCF-mediated recruitment of TLE/Groucho proteins, but the molecular basis for TLE/TCF-dependent repression is unclear. We describe the unusual three-dimensional structure of the N-terminal Q domain of TLE1 that mediates tetramerization and binds to TCFs. We find that differences in repression potential of TCF/LEFs correlates with their affinities for TLE-Q, rather than direct competition between beta-catenin and TLE for TCFs as part of an activation-repression switch. Structure-based mutation of the TLE tetramer interface shows that dimers cannot mediate repression, even though they bind to TCFs with the same affinity as tetramers. Furthermore, the TLE Q tetramer, not the dimer, binds to chromatin, specifically to K20 methylated histone H4 tails, suggesting that the TCF/TLE tetramer complex promotes structural transitions of chromatin to mediate repression.
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| - | Molecular functions of the TLE tetramerization domain in Wnt target gene repression.,Chodaparambil JV, Pate KT, Hepler MR, Tsai BP, Muthurajan UM, Luger K, Waterman ML, Weis WI EMBO J. 2014 Apr 1;33(7):719-31. doi: 10.1002/embj.201387188. Epub 2014 Mar 3. PMID:24596249<ref>PMID:24596249</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 4om3" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chodaparambil, J V]] | + | [[Category: Large Structures]] |
| - | [[Category: Weis, W I]] | + | [[Category: Chodaparambil JV]] |
| - | [[Category: Dna binding]] | + | [[Category: Weis WI]] |
| - | [[Category: Helix-turn-helix]]
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| - | [[Category: Tcf/lef]]
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| - | [[Category: Tetramer]]
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| - | [[Category: Transcription]]
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| - | [[Category: Wnt repressor]]
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