|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Solution structure of MLL4 PHD6 domain in complex with histone H4K16ac peptide== | | ==Solution structure of MLL4 PHD6 domain in complex with histone H4K16ac peptide== |
| - | <StructureSection load='6o7g' size='340' side='right'caption='[[6o7g]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='6o7g' size='340' side='right'caption='[[6o7g]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6o7g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O7G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O7G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6o7g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O7G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O7G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KMT2D, ALR, MLL2, MLL4 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=6o7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o7g OCA], [https://pdbe.org/6o7g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o7g RCSB], [https://www.ebi.ac.uk/pdbsum/6o7g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o7g ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=6o7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o7g OCA], [http://pdbe.org/6o7g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o7g RCSB], [http://www.ebi.ac.uk/pdbsum/6o7g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o7g ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/KMT2D_HUMAN KMT2D_HUMAN]] Kabuki syndrome. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/KMT2D_HUMAN KMT2D_HUMAN] Kabuki syndrome. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KMT2D_HUMAN KMT2D_HUMAN]] Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription.<ref>PMID:16603732</ref> <ref>PMID:17500065</ref> <ref>PMID:17851529</ref> | + | [https://www.uniprot.org/uniprot/KMT2D_HUMAN KMT2D_HUMAN] Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription.<ref>PMID:16603732</ref> <ref>PMID:17500065</ref> <ref>PMID:17851529</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 21: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6o7g" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6o7g" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Histone 3D structures|Histone 3D structures]] |
| | + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Histone-lysine N-methyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kutateladze, T G]] | + | [[Category: Kutateladze TG]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang Y]] |
| - | [[Category: Acetylation]]
| + | |
| - | [[Category: Chromatin]]
| + | |
| - | [[Category: H4k16ac]]
| + | |
| - | [[Category: Histone]]
| + | |
| - | [[Category: Mll4]]
| + | |
| - | [[Category: Mof]]
| + | |
| - | [[Category: Phd finger]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Disease
KMT2D_HUMAN Kabuki syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
KMT2D_HUMAN Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription.[1] [2] [3]
Publication Abstract from PubMed
Histone methyltransferase MLL4 is centrally involved in transcriptional regulation and is often mutated in human diseases, including cancer and developmental disorders. MLL4 contains a catalytic SET domain that mono-methylates histone H3K4 and seven PHD fingers of unclear function. Here, we identify the PHD6 finger of MLL4 (MLL4-PHD6) as a selective reader of the epigenetic modification H4K16ac. The solution NMR structure of MLL4-PHD6 in complex with a H4K16ac peptide along with binding and mutational analyses reveal unique mechanistic features underlying recognition of H4K16ac. Genomic studies show that one third of MLL4 chromatin binding sites overlap with H4K16ac-enriched regions in vivo and that MLL4 occupancy in a set of genomic targets depends on the acetyltransferase activity of MOF, a H4K16ac-specific acetyltransferase. The recognition of H4K16ac is conserved in the PHD7 finger of paralogous MLL3. Together, our findings reveal a previously uncharacterized acetyllysine reader and suggest that selective targeting of H4K16ac by MLL4 provides a direct functional link between MLL4, MOF and H4K16 acetylation.
Selective binding of the PHD6 finger of MLL4 to histone H4K16ac links MLL4 and MOF.,Zhang Y, Jang Y, Lee JE, Ahn J, Xu L, Holden MR, Cornett EM, Krajewski K, Klein BJ, Wang SP, Dou Y, Roeder RG, Strahl BD, Rothbart SB, Shi X, Ge K, Kutateladze TG Nat Commun. 2019 May 24;10(1):2314. doi: 10.1038/s41467-019-10324-8. PMID:31127101[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mo R, Rao SM, Zhu YJ. Identification of the MLL2 complex as a coactivator for estrogen receptor alpha. J Biol Chem. 2006 Jun 9;281(23):15714-20. Epub 2006 Apr 7. PMID:16603732 doi:http://dx.doi.org/M513245200
- ↑ Cho YW, Hong T, Hong S, Guo H, Yu H, Kim D, Guszczynski T, Dressler GR, Copeland TD, Kalkum M, Ge K. PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex. J Biol Chem. 2007 Jul 13;282(28):20395-406. Epub 2007 May 11. PMID:17500065 doi:http://dx.doi.org/M701574200
- ↑ Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007 Oct 11;449(7163):689-94. Epub 2007 Sep 12. PMID:17851529 doi:http://dx.doi.org/10.1038/nature06192
- ↑ Zhang Y, Jang Y, Lee JE, Ahn J, Xu L, Holden MR, Cornett EM, Krajewski K, Klein BJ, Wang SP, Dou Y, Roeder RG, Strahl BD, Rothbart SB, Shi X, Ge K, Kutateladze TG. Selective binding of the PHD6 finger of MLL4 to histone H4K16ac links MLL4 and MOF. Nat Commun. 2019 May 24;10(1):2314. doi: 10.1038/s41467-019-10324-8. PMID:31127101 doi:http://dx.doi.org/10.1038/s41467-019-10324-8
|
