View source for 8ejp


==Crystal structure of the homeodomain of Platypus sDUX in complex with DNA containing 5-Bromouracil==
<StructureSection load='8ejp' size='340' side='right'caption='[[8ejp]], [[Resolution|resolution]] 2.17&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ejp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Ornithorhynchus_anatinus Ornithorhynchus anatinus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EJP 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]] 2.174&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BRU:5-BROMO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>BRU</scene>, <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=8ejp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ejp OCA], [https://pdbe.org/8ejp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ejp RCSB], [https://www.ebi.ac.uk/pdbsum/8ejp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ejp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A6I8NF41_ORNAN A0A6I8NF41_ORNAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Double homeobox (DUX) genes are unique to eutherian mammals, expressed transiently during zygotic genome activation (ZGA) and involved in facioscapulohumeral muscular dystrophy (FSHD) and cancer when misexpressed. We evaluate the 3 human DUX genes and the ancestral single homeobox gene sDUX from the non-eutherian mammal, platypus, and find that DUX4 cytotoxicity is not shared with DUXA or DUXB, but surprisingly is shared with platypus sDUX, which binds DNA as a homodimer and activates numerous ZGA genes and long terminal repeat (LTR) elements. DUXA, although transcriptionally inactive, has DNA binding overlap with DUX4, and DUXA-VP64 activates DUX4 targets and is cytotoxic. DUXA competition antagonizes the activity of DUX4 on its target genes, including in FSHD patient cells. Since DUXA is a DUX4 target gene, this competition potentiates feedback inhibition, constraining the window of DUX4 activity. The DUX gene family therefore comprises antagonistic members of opposing function, with implications for their roles in ZGA, FSHD, and cancer.

Antagonism among DUX family members evolved from an ancestral toxic single homeodomain protein.,Bosnakovski D, Toso EA, Ener ET, Gearhart MD, Yin L, Luttmann FF, Magli A, Shi K, Kim J, Aihara H, Kyba M iScience. 2023 Sep 2;26(10):107823. doi: 10.1016/j.isci.2023.107823. eCollection , 2023 Oct 20. PMID:37744032<ref>PMID:37744032</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ejp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ornithorhynchus anatinus]]
[[Category: Aihara H]]
[[Category: Shi K]]
[[Category: Yin L]]