View source for 4hga


==Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX==
<StructureSection load='4hga' size='340' side='right'caption='[[4hga]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4hga]] is a 3 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=4HGA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HGA 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]] 2.799&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PC4:TETRACHLOROPLATINATE(II)'>PC4</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=4hga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hga OCA], [https://pdbe.org/4hga PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hga RCSB], [https://www.ebi.ac.uk/pdbsum/4hga PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hga ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DAXX_HUMAN DAXX_HUMAN] Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Down-regulates basal and activated transcription. Seems to act as a transcriptional corepressor and inhibits PAX3 and ETS1 through direct protein-protein interaction. Modulates PAX5 activity. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively.<ref>PMID:12140263</ref> <ref>PMID:15364927</ref> <ref>PMID:17081986</ref> <ref>PMID:16845383</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mammalian histone H3.3 is a variant of the canonical H3.1 essential for genome reprogramming in fertilized eggs and maintenance of chromatin structure in neuronal cells. An H3.3-specific histone chaperone, DAXX, directs the deposition of H3.3 onto pericentric and telomeric heterochromatin. H3.3 differs from H3.1 by only five amino acids, yet DAXX can distinguish the two with high precision. By a combination of structural, biochemical and cell-based targeting analyses, we show that Ala87 and Gly90 are the principal determinants of human H3.3 specificity. DAXX uses a shallow hydrophobic pocket to accommodate the small hydrophobic Ala87 of H3.3, whereas a polar binding environment in DAXX prefers Gly90 in H3.3 over the hydrophobic Met90 in H3.1. An H3.3-H4 heterodimer is bound by the histone-binding domain of DAXX, which makes extensive contacts with both H3.3 and H4.

Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX.,Liu CP, Xiong C, Wang M, Yu Z, Yang N, Chen P, Zhang Z, Li G, Xu RM Nat Struct Mol Biol. 2012 Dec;19(12):1287-92. doi: 10.1038/nsmb.2439. Epub 2012, Nov 11. PMID:23142979<ref>PMID:23142979</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4hga" style="background-color:#fffaf0;"></div>

==See Also==
*[[Death-associated protein 3D structures|Death-associated protein 3D structures]]
*[[Histone 3D structures|Histone 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen P]]
[[Category: Li GH]]
[[Category: Liu CP]]
[[Category: Wang MZ]]
[[Category: Xiong CY]]
[[Category: Xu RM]]
[[Category: Yang N]]
[[Category: Yu ZL]]
[[Category: Zhang ZG]]