6nj9

From Proteopedia

(Difference between revisions)

Revision as of 06:01, 20 May 2020

Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 2-to-1 complex

6nj9, resolution 2.96Å

Structural highlights

6nj9 is a 12 chain structure with sequence from [1], African clawed frog and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	DOT1L, KIAA1814, KMT4 (HUMAN), UBB (HUMAN)
Activity:	[Histone_H3-lysine(79)_N-trimethyltransferase [Histone H3]-lysine(79) N-trimethyltransferase], with EC number 2.1.1.360
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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. [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. [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. [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. [DOT1L_HUMAN] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.

Publication Abstract from PubMed

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.

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^[1]

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

References

↑ Worden EJ, Hoffmann NA, Hicks CW, Wolberger C. Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L. Cell. 2019 Feb 8. pii: S0092-8674(19)30151-5. doi: 10.1016/j.cell.2019.02.002. PMID:30765112 doi:http://dx.doi.org/10.1016/j.cell.2019.02.002

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/6nj9"

@@ Line 7: / Line 7: @@
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DOT1L, KIAA1814, KMT4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Histone_H3]-lysine(79)_N-trimethyltransferase [Histone H3]-lysine(79) N-trimethyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.360 2.1.1.360] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6nj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nj9 OCA], [http://pdbe.org/6nj9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nj9 RCSB], [http://www.ebi.ac.uk/pdbsum/6nj9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nj9 ProSAT]</span></td></tr>
 </table>
@@ Line 30: / Line 30: @@
 </SX>
 [[Category: African clawed frog]]
-[[Category: Histone-lysine N-methyltransferase]]
 [[Category: Human]]
 [[Category: Large Structures]]

6nj9

From Proteopedia

Revision as of 06:01, 20 May 2020

Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 2-to-1 complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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