4uuv: Difference between revisions
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==Structure of the DNA binding ETS domain of human ETV4 in complex with DNA== | ==Structure of the DNA binding ETS domain of human ETV4 in complex with DNA== | ||
<StructureSection load='4uuv' size='340' side='right' caption='[[4uuv]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='4uuv' size='340' side='right'caption='[[4uuv]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4uuv]] is a 24 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UUV OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4uuv]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=4UUV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UUV FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</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=4uuv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uuv OCA], [https://pdbe.org/4uuv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uuv RCSB], [https://www.ebi.ac.uk/pdbsum/4uuv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uuv ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/ETV4_HUMAN ETV4_HUMAN] Ewing sarcoma. | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ETV4_HUMAN ETV4_HUMAN] Transcriptional activator that binds to the enhancer of the adenovirus E1A gene; the core-binding sequence is 5'[AC]GGA[AT]GT-3'.<ref>PMID:19307308</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Ets transcription factors, which share the conserved Ets DNA-binding domain, number nearly 30 members in humans and are particularly involved in developmental processes. Their deregulation following changes in expression, transcriptional activity, or by chromosomal translocation, plays a critical role in carcinogenesis. Ets DNA-binding, selectivity and regulation have been extensively studied, although questions still arise regarding binding specificity outside the core GGA recognition sequence, and the mode of action of Ets post-translational modifications. Here we report the crystal structures of ETV1, ETV4, ETV5 and FEV, alone and in complex with DNA. We identify previously unrecognized features of the protein-DNA interface. Interactions with the DNA backbone account for most of the binding affinity. We describe a highly coordinated network of water molecules acting in base selection upstream of the GGAA core, and the structural features that may account for discrimination against methylated cytidine residues. Unexpectedly, all proteins crystallized as disulfide-linked dimers, exhibiting a novel interface (distant to the DNA recognition helix). Homodimers of ETV1, ETV4 and ETV5 could be reduced to monomers, leading to a 40-200-fold increase in DNA binding affinity. Hence, we present the first indication of a redox-dependent regulatory mechanism which may control the activity of this subset of oncogenic Ets transcription factors. | |||
Structures of the Ets Domains of Transcription Factors ETV1, ETV4, ETV5 and FEV: Determinants of DNA Binding and Redox Regulation by Disulfide bond formation.,Cooper CD, Newman JA, Aitkenhead H, Allerston CK, Gileadi O J Biol Chem. 2015 Apr 12. pii: jbc.M115.646737. PMID:25866208<ref>PMID:25866208</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4uuv" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: | [[Category: Arrowsmith CH]] | ||
[[Category: Edwards | [[Category: Bountra C]] | ||
[[Category: Gileadi | [[Category: Cooper CDO]] | ||
[[Category: Kopec | [[Category: Edwards AM]] | ||
[[Category: Newman | [[Category: Gileadi O]] | ||
[[Category: | [[Category: Kopec J]] | ||
[[Category: Newman JA]] | |||
[[Category: Von Delft F]] | |||