2md5: Difference between revisions
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New page: '''Unreleased structure''' The entry 2md5 is ON HOLD Authors: De, S., McIntosh, L.P., Chan, A.C. K., Coyne, H.J., Okon, M., Graves, B.J., Murphy, M.E. P. Description: Structure of unin... |
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==Structure of uninhibited ETV6 ETS domain== | |||
<StructureSection load='2md5' size='340' side='right'caption='[[2md5]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2md5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ETV6_MOUSE ETV6_MOUSE] Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:24333486</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2md5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Chan AC]] | |||
[[Category: Coyne HJ]] | |||
[[Category: De S]] | |||
[[Category: Graves BJ]] | |||
[[Category: Mcintosh LP]] | |||
[[Category: Murphy ME]] | |||
[[Category: Okon M]] | |||
Latest revision as of 06:04, 15 May 2024
Structure of uninhibited ETV6 ETS domain
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