4hga

From Proteopedia

(Difference between revisions)

Revision as of 15:45, 4 August 2016

Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX

Structural highlights

4hga is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	DAXX, BING2, DAP6 (HUMAN), H3F3A, H3.3A, H3F3, PP781, H3F3B, H3.3B (HUMAN), HIST1H4A, H4/A, H4FA, HIST1H4B, H4/I, H4FI, HIST1H4C, H4/G, H4FG, HIST1H4D, H4/B, H4FB, HIST1H4E, H4/J, H4FJ, HIST1H4F, H4/C, H4FC, HIST1H4H, H4/H, H4FH, HIST1H4I, H4/M, H4FM, HIST1H4J, H4/E, H4FE, HIST1H4K, H4/D, H4FD, HIST1H4L, H4/K, H4FK, HIST2H4A, H4/N, H4F2, H4FN, HIST2H4, HIST2H4B, H4/O, H4FO, HIST4H4 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hollenbach AD, McPherson CJ, Mientjes EJ, Iyengar R, Grosveld G. Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek. J Cell Sci. 2002 Aug 15;115(Pt 16):3319-30. PMID:12140263
↑ Zhao LY, Liu J, Sidhu GS, Niu Y, Liu Y, Wang R, Liao D. Negative regulation of p53 functions by Daxx and the involvement of MDM2. J Biol Chem. 2004 Nov 26;279(48):50566-79. Epub 2004 Sep 10. PMID:15364927 doi:10.1074/jbc.M406743200
↑ Lin DY, Huang YS, Jeng JC, Kuo HY, Chang CC, Chao TT, Ho CC, Chen YC, Lin TP, Fang HI, Hung CC, Suen CS, Hwang MJ, Chang KS, Maul GG, Shih HM. Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol Cell. 2006 Nov 3;24(3):341-54. PMID:17081986 doi:10.1016/j.molcel.2006.10.019
↑ Tang J, Qu LK, Zhang J, Wang W, Michaelson JS, Degenhardt YY, El-Deiry WS, Yang X. Critical role for Daxx in regulating Mdm2. Nat Cell Biol. 2006 Aug;8(8):855-62. Epub 2006 Jul 16. PMID:16845383 doi:10.1038/ncb1442
↑ Liu CP, Xiong C, Wang M, Yu Z, Yang N, Chen P, Zhang Z, Li G, Xu RM. Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX. Nat Struct Mol Biol. 2012 Dec;19(12):1287-92. doi: 10.1038/nsmb.2439. Epub 2012, Nov 11. PMID:23142979 doi:http://dx.doi.org/10.1038/nsmb.2439

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4hga"

@@ Line 1: / Line 1: @@
 ==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=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PC4:TETRACHLOROPLATINATE(II)'>PC4</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DAXX, BING2, DAP6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), H3F3A, H3.3A, H3F3, PP781, H3F3B, H3.3B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HIST1H4A, H4/A, H4FA, HIST1H4B, H4/I, H4FI, HIST1H4C, H4/G, H4FG, HIST1H4D, H4/B, H4FB, HIST1H4E, H4/J, H4FJ, HIST1H4F, H4/C, H4FC, HIST1H4H, H4/H, H4FH, HIST1H4I, H4/M, H4FM, HIST1H4J, H4/E, H4FE, HIST1H4K, H4/D, H4FD, HIST1H4L, H4/K, H4FK, HIST2H4A, H4/N, H4F2, H4FN, HIST2H4, HIST2H4B, H4/O, H4FO, HIST4H4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hga OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hga RCSB], [http://www.ebi.ac.uk/pdbsum/4hga PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hga OCA], [http://pdbe.org/4hga PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hga RCSB], [http://www.ebi.ac.uk/pdbsum/4hga PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hga ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 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==

4hga

From Proteopedia

Revision as of 15:45, 4 August 2016

Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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