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| ==Crystal structure of ETV6 bound to a specific DNA sequence== | | ==Crystal structure of ETV6 bound to a specific DNA sequence== |
| <StructureSection load='4mhg' size='340' side='right' caption='[[4mhg]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='4mhg' size='340' side='right'caption='[[4mhg]], [[Resolution|resolution]] 2.20Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4mhg]] is a 3 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=4MHG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MHG FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4mhg]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MHG FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lf8|2lf8]], [[2lf7|2lf7]]</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]] 2.199Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Etv6, Tel, Tel1 ([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=4mhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mhg OCA], [https://pdbe.org/4mhg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mhg RCSB], [https://www.ebi.ac.uk/pdbsum/4mhg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mhg 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=4mhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mhg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mhg RCSB], [http://www.ebi.ac.uk/pdbsum/4mhg PDBsum]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/ETV6_MOUSE ETV6_MOUSE]] Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. | | [https://www.uniprot.org/uniprot/ETV6_MOUSE ETV6_MOUSE] Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| DNA binding by the ETS transcriptional repressor ETV6 (or TEL) is auto-inhibited~50-fold due to an alpha-helix that sterically blocks its ETS domain binding interface. Using NMR spectroscopy, we demonstrate that this marginally-stable helix is unfolded, and not displaced to a non-inhibitory position, when ETV6 is bound to DNA containing a consensus 5'GGAA3' recognition site. Although significantly lower in affinity, binding to non-specific DNA is auto-inhibited~5-fold and also accompanied by helix unfolding. Based on NMR chemical shift perturbations, both specific and non-specific DNA are bound via the same canonical ETS domain interface. However, spectral perturbations are smaller for the non-specific complex, suggesting weaker and less well-defined interactions than in the specific complex. In parallel, the crystal structure of ETV6 bound to a specific DNA duplex was determined. The structure of this complex reveals that a non-conserved histidine residue in the ETS domain recognition helix helps establish the specificity of ETV6 for DNA-binding sites containing 5'GGAA3' versus 5'GGAT3'. These studies provide a unified steric mechanism for attenuating ETV6 binding to both specific and non-specific DNA and expand the repertoire of characterized auto-inhibitory strategies utilized to regulate ETS factors.
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| Steric mechanism of auto-inhibitory regulation of specific and non-specific DNA binding by the ETS transcriptional repressor ETV6.,De S, Chan AC, Coyne HJ 3rd, Bhachech N, Hermsdorf U, Okon M, Murphy ME, Graves BJ, McIntosh LP J Mol Biol. 2013 Dec 11. pii: S0022-2836(13)00747-X. doi:, 10.1016/j.jmb.2013.11.031. PMID:24333486<ref>PMID:24333486</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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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Lk3 transgenic mice]] | | [[Category: Large Structures]] |
| [[Category: Chan, A C]] | | [[Category: Mus musculus]] |
| [[Category: De, S]] | | [[Category: Synthetic construct]] |
| [[Category: Graves, B J]] | | [[Category: Chan AC]] |
| [[Category: III, H J.Coyne]] | | [[Category: Coyne III HJ]] |
| [[Category: McIntosh, L P]] | | [[Category: De S]] |
| [[Category: Murphy, M E]] | | [[Category: Graves BJ]] |
| [[Category: Okon, M]] | | [[Category: McIntosh LP]] |
| [[Category: Ets domain]] | | [[Category: Murphy ME]] |
| [[Category: Transcription factor]] | | [[Category: Okon M]] |
| [[Category: Transcription-dna complex]]
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