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| | ==Structure of uninhibited ETV6 ETS domain== | | ==Structure of uninhibited ETV6 ETS domain== |
| - | <StructureSection load='2md5' size='340' side='right' caption='[[2md5]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2md5' size='340' side='right'caption='[[2md5]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2md5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MD5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MD5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2md5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MD5 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lf8|2lf8]], [[2lf7|2lf7]], [[4mhg|4mhg]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2lf8|2lf8]], [[2lf7|2lf7]], [[4mhg|4mhg]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Etv6, Tel, Tel1 ([https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2md5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2md5 OCA], [http://pdbe.org/2md5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2md5 RCSB], [http://www.ebi.ac.uk/pdbsum/2md5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2md5 ProSAT]</span></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=2md5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2md5 OCA], [https://pdbe.org/2md5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2md5 RCSB], [https://www.ebi.ac.uk/pdbsum/2md5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2md5 ProSAT]</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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Chan, A C]] | | [[Category: Chan, A C]] |
| Structural highlights
Function
[ETV6_MOUSE] Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ De S, Chan AC, Coyne HJ 3rd, Bhachech N, Hermsdorf U, Okon M, Murphy ME, Graves BJ, McIntosh LP. Steric mechanism of auto-inhibitory regulation of specific and non-specific DNA binding by the ETS transcriptional repressor ETV6. J Mol Biol. 2013 Dec 11. pii: S0022-2836(13)00747-X. doi:, 10.1016/j.jmb.2013.11.031. PMID:24333486 doi:http://dx.doi.org/10.1016/j.jmb.2013.11.031
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