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| | ==Poised-state Dot1L bound to the H2B-Ubiquitinated nucleosome== | | ==Poised-state Dot1L bound to the H2B-Ubiquitinated nucleosome== |
| - | <StructureSection load='6nog' size='340' side='right'caption='[[6nog]], [[Resolution|resolution]] 3.90Å' scene=''> | + | <SX load='6nog' size='340' side='right' viewer='molstar' caption='[[6nog]], [[Resolution|resolution]] 3.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nog]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/ ], [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NOG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NOG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nog]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NOG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NOG FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DOT1L, KIAA1814, KMT4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=6nog FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nog OCA], [https://pdbe.org/6nog PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nog RCSB], [https://www.ebi.ac.uk/pdbsum/6nog PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nog ProSAT]</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=6nog FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nog OCA], [http://pdbe.org/6nog PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nog RCSB], [http://www.ebi.ac.uk/pdbsum/6nog PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nog ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN]] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA. [[http://www.uniprot.org/uniprot/H2A1_XENLA H2A1_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [[http://www.uniprot.org/uniprot/H4_XENLA H4_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [[http://www.uniprot.org/uniprot/H32_XENLA H32_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [[http://www.uniprot.org/uniprot/H2B11_XENLA H2B11_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. | + | [https://www.uniprot.org/uniprot/H32_XENLA H32_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Methylation of histone H3 K79 by Dot1L is a hallmark of actively transcribed genes that depends on monoubiquitination of H2B K120 (H2B-Ub) and is an example of histone modification cross-talk that is conserved from yeast to humans. We report here cryo-EM structures of Dot1L bound to ubiquitinated nucleosome that show how H2B-Ub stimulates Dot1L activity and reveal a role for the histone H4 tail in positioning Dot1L. We find that contacts mediated by Dot1L and the H4 tail induce a conformational change in the globular core of histone H3 that reorients K79 from an inaccessible position, thus enabling this side chain to insert into the active site in a position primed for catalysis. Our study provides a comprehensive mechanism of cross-talk between histone ubiquitination and methylation and reveals structural plasticity in histones that makes it possible for histone-modifying enzymes to access residues within the nucleosome core.
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| - | Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L.,Worden EJ, Hoffmann NA, Hicks CW, Wolberger C Cell. 2019 Feb 8. pii: S0092-8674(19)30151-5. doi: 10.1016/j.cell.2019.02.002. PMID:30765112<ref>PMID:30765112</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6nog" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
| | *[[Histone 3D structures|Histone 3D structures]] | | *[[Histone 3D structures|Histone 3D structures]] |
| | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] | | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| - | [[Category: African clawed frog]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Histone-lysine N-methyltransferase]]
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| - | [[Category: Human]]
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hoffmann, N A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Wolberger, C]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Worden, E J]] | + | [[Category: Hoffmann NA]] |
| - | [[Category: Methyltransferase]] | + | [[Category: Wolberger C]] |
| - | [[Category: Nucleosome]] | + | [[Category: Worden EJ]] |
| - | [[Category: Structural protein-transferase-dna complex]]
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| - | [[Category: Ubiquitin]]
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