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5d6y

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Revision as of 16:45, 15 November 2017

Crystal structure of double tudor domain of human lysine demethylase KDM4A complexed with histone H3K23me3

Structural highlights

5d6y is a 10 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	5d6x, 5d6w
Gene:	KDM4A, JHDM3A, JMJD2, JMJD2A, KIAA0677 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KDM4A_HUMAN] Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.^[1] ^[2] ^[3] Isoform 2: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain.^[4] ^[5] ^[6]

Publication Abstract from PubMed

The KDM4 histone demethylases are conserved epigenetic regulators linked to development, spermatogenesis and tumorigenesis. However, how the KDM4 family targets specific chromatin regions is largely unknown. Here, an extensive histone peptide microarray analysis uncovers trimethyl-lysine histone-binding preferences among the closely related KDM4 double tudor domains (DTDs). KDM4A/B DTDs bind strongly to H3K23me3, a poorly understood histone modification recently shown to be enriched in meiotic chromatin of ciliates and nematodes. The 2.28 A co-crystal structure of KDM4A-DTD in complex with H3K23me3 peptide reveals key intermolecular interactions for H3K23me3 recognition. Furthermore, analysis of the 2.56 A KDM4B-DTD crystal structure pinpoints the underlying residues required for exclusive H3K23me3 specificity, an interaction supported by in vivo co-localization of KDM4B and H3K23me3 at heterochromatin in mammalian meiotic and newly postmeiotic spermatocytes. In vitro demethylation assays suggest H3K23me3 binding by KDM4B stimulates H3K36 demethylation. Together, these results provide a possible mechanism whereby H3K23me3-binding by KDM4B directs localized H3K36 demethylation during meiosis and spermatogenesis.

Reader domain specificity and lysine demethylase-4 family function.,Su Z, Wang F, Lee JH, Stephens KE, Papazyan R, Voronina E, Krautkramer KA, Raman A, Thorpe JJ, Boersma MD, Kuznetsov VI, Miller MD, Taverna SD, Phillips GN Jr, Denu JM Nat Commun. 2016 Nov 14;7:13387. doi: 10.1038/ncomms13387. PMID:27841353^[7]

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

References

↑ Zhang D, Yoon HG, Wong J. JMJD2A is a novel N-CoR-interacting protein and is involved in repression of the human transcription factor achaete scute-like homologue 2 (ASCL2/Hash2). Mol Cell Biol. 2005 Aug;25(15):6404-14. PMID:16024779 doi:http://dx.doi.org/25/15/6404
↑ Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006 May 5;125(3):467-81. Epub 2006 Apr 6. PMID:16603238 doi:10.1016/j.cell.2006.03.028
↑ Verrier L, Escaffit F, Chailleux C, Trouche D, Vandromme M. A new isoform of the histone demethylase JMJD2A/KDM4A is required for skeletal muscle differentiation. PLoS Genet. 2011 Jun;7(6):e1001390. doi: 10.1371/journal.pgen.1001390. Epub 2011 , Jun 2. PMID:21694756 doi:http://dx.doi.org/10.1371/journal.pgen.1001390
↑ Zhang D, Yoon HG, Wong J. JMJD2A is a novel N-CoR-interacting protein and is involved in repression of the human transcription factor achaete scute-like homologue 2 (ASCL2/Hash2). Mol Cell Biol. 2005 Aug;25(15):6404-14. PMID:16024779 doi:http://dx.doi.org/25/15/6404
↑ Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006 May 5;125(3):467-81. Epub 2006 Apr 6. PMID:16603238 doi:10.1016/j.cell.2006.03.028
↑ Verrier L, Escaffit F, Chailleux C, Trouche D, Vandromme M. A new isoform of the histone demethylase JMJD2A/KDM4A is required for skeletal muscle differentiation. PLoS Genet. 2011 Jun;7(6):e1001390. doi: 10.1371/journal.pgen.1001390. Epub 2011 , Jun 2. PMID:21694756 doi:http://dx.doi.org/10.1371/journal.pgen.1001390
↑ Su Z, Wang F, Lee JH, Stephens KE, Papazyan R, Voronina E, Krautkramer KA, Raman A, Thorpe JJ, Boersma MD, Kuznetsov VI, Miller MD, Taverna SD, Phillips GN Jr, Denu JM. Reader domain specificity and lysine demethylase-4 family function. Nat Commun. 2016 Nov 14;7:13387. doi: 10.1038/ncomms13387. PMID:27841353 doi:http://dx.doi.org/10.1038/ncomms13387

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5d6y"

@@ Line 3: / Line 3: @@
 <StructureSection load='5d6y' size='340' side='right' caption='[[5d6y]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5d6y]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D6Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D6Y FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5d6y]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D6Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D6Y FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5d6x|5d6x]], [[5d6w|5d6w]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KDM4A, JHDM3A, JMJD2, JMJD2A, KIAA0677 ([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=5d6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d6y OCA], [http://pdbe.org/5d6y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d6y RCSB], [http://www.ebi.ac.uk/pdbsum/5d6y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d6y ProSAT]</span></td></tr>
 </table>
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5d6y" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Jumonji domain-containing protein|Jumonji domain-containing protein]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Denu, J M]]
 [[Category: Miller, M D]]

5d6y

From Proteopedia

Revision as of 16:45, 15 November 2017

Crystal structure of double tudor domain of human lysine demethylase KDM4A complexed with histone H3K23me3

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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