View source for 4avp


==Crystal structure of the DNA-binding domain of human ETV1.==
<StructureSection load='4avp' size='340' side='right'caption='[[4avp]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4avp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AVP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AVP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.82&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=4avp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4avp OCA], [https://pdbe.org/4avp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4avp RCSB], [https://www.ebi.ac.uk/pdbsum/4avp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4avp ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ETV1_HUMAN ETV1_HUMAN] Ewing sarcoma. Ewing sarcoma (ES) [MIM:[https://omim.org/entry/612219 612219]: A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving ETV1 is found in patients with Erwing sarcoma. Translocation t(7;22)(p22;q12) with EWSR1.
== Function ==
[https://www.uniprot.org/uniprot/ETV1_HUMAN ETV1_HUMAN] Transcriptional activator that binds to DNA sequences containing the consensus pentanucleotide 5'-CGGA[AT]-3'.
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4avp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Allerston CK]]
[[Category: Arrowsmith CH]]
[[Category: Bountra C]]
[[Category: Canning P]]
[[Category: Chaikuad A]]
[[Category: Cooper CDO]]
[[Category: Edwards A]]
[[Category: Filippakopoulos P]]
[[Category: Gileadi O]]
[[Category: Krojer T]]
[[Category: Von Delft F]]