4mhg: Difference between revisions
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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=''> | ||
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</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lf8|2lf8]], [[2lf7|2lf7]]</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 ([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'>[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> | <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://pdbe.org/4mhg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mhg RCSB], [http://www.ebi.ac.uk/pdbsum/4mhg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mhg ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4mhg" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 01:48, 5 August 2016
Crystal structure of ETV6 bound to a specific DNA sequenceCrystal structure of ETV6 bound to a specific DNA sequence
Structural highlights
Function[ETV6_MOUSE] Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. Publication Abstract from PubMedDNA 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
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