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6o96

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Revision as of 06:37, 19 June 2019

Dot1L bound to the H2BK120 Ubiquitinated nucleosome

Structural highlights

6o96 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:	hist1h2aj, LOC494591, XELAEV_18003602mg (African clawed frog), DOT1L, KIAA1814, KMT4 (HUMAN), UBB (HUMAN)
Activity:	Histone-lysine N-methyltransferase, with EC number 2.1.1.43
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

Publication Abstract from PubMed

The essential histone H3 lysine 79 methyltransferase Dot1L regulates transcription and genomic stability and is deregulated in leukemia. The activity of Dot1L is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120Ub); however, the detailed mechanism is not understood. We report cryo-EM structures of human Dot1L bound to (1) H2BK120Ub and (2) unmodified nucleosome substrates at 3.5 A and 4.9 A, respectively. Comparison of both structures, complemented with biochemical experiments, provides critical insights into the mechanism of Dot1L stimulation by H2BK120Ub. Both structures show Dot1L binding to the same extended surface of the histone octamer. In yeast, this surface is used by silencing proteins involved in heterochromatin formation, explaining the mechanism of their competition with Dot1. These results provide a strong foundation for understanding conserved crosstalk between histone modifications found at actively transcribed genes and offer a general model of how ubiquitin might regulate the activity of chromatin enzymes.

Structural Basis of Dot1L Stimulation by Histone H2B Lysine 120 Ubiquitination.,Valencia-Sanchez MI, De Ioannes P, Wang M, Vasilyev N, Chen R, Nudler E, Armache JP, Armache KJ Mol Cell. 2019 Apr 8. pii: S1097-2765(19)30233-3. doi:, 10.1016/j.molcel.2019.03.029. PMID:30981630^[1]

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

References

↑ Valencia-Sanchez MI, De Ioannes P, Wang M, Vasilyev N, Chen R, Nudler E, Armache JP, Armache KJ. Structural Basis of Dot1L Stimulation by Histone H2B Lysine 120 Ubiquitination. Mol Cell. 2019 Apr 8. pii: S1097-2765(19)30233-3. doi:, 10.1016/j.molcel.2019.03.029. PMID:30981630 doi:http://dx.doi.org/10.1016/j.molcel.2019.03.029

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/6o96"

@@ Line 3: / Line 3: @@
 <StructureSection load='6o96' size='340' side='right'caption='[[6o96]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6o96]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O96 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6o96]] 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=6O96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O96 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hist1h2aj, LOC494591, XELAEV_18003602mg ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog]), 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='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=6o96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o96 OCA], [http://pdbe.org/6o96 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o96 RCSB], [http://www.ebi.ac.uk/pdbsum/6o96 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o96 ProSAT]</span></td></tr>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: African clawed frog]]
 [[Category: Histone-lysine N-methyltransferase]]
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Armache, J P]]

6o96

From Proteopedia

Revision as of 06:37, 19 June 2019

Dot1L bound to the H2BK120 Ubiquitinated nucleosome

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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