6ine

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Revision as of 07:34, 23 May 2019

Crystal Structure of human ASH1L-MRG15 complex

Structural highlights

6ine is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	ASH1L, KIAA1420, KMT2H (HUMAN), MORF4L1, MRG15, FWP006, HSPC008, HSPC061, PP368 (HUMAN)
Activity:	Histone-lysine N-methyltransferase, with EC number 2.1.1.43
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ASH1L_HUMAN] Histone methyltransferase specifically methylating 'Lys-36' of histone H3 (H3K36me).^[1] [MO4L1_HUMAN] Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Also component of the mSin3A complex which acts to repress transcription by deacetylation of nucleosomal histones. Required for homologous recombination repair (HRR) and resistance to mitomycin C (MMC). Involved in the localization of PALB2, BRCA2 and RAD51, but not BRCA1, to DNA-damage foci.^[2] ^[3]

Publication Abstract from PubMed

The evolutionarily conserved Trithorax group protein Ash1 is a SET domain histone methyltransferase that mono- and dimethylates lysine 36 of histone H3 (H3K36). Ash1 forms a complex with Mrg15 and Nurf55, and the binding of Mrg15 greatly stimulates the catalytic activity of Ash1, yet the underlying molecular mechanisms remain unknown. Here we report the crystal structure of the tandem Mrg15-interacting and SET domains of human Ash1L in complex with Mrg15. Ash1L interacts with Mrg15 principally via a segment located N-terminal to the catalytic SET domain. Surprisingly, an autoinhibitory loop in the post-SET region of Ash1L is destabilized on Mrg15 binding despite no direct contact. Dynamics of the autoinhibitory loop can be attributed to subtle structural changes of the S-adenosylmethionine (SAM) binding pocket induced by Mrg15 binding, implicating a mechanism of conformational coupling between SAM and substrate binding sites. The findings broaden the understanding of regulation of H3K36 methyltransferases.

Structural Insights into Stimulation of Ash1L's H3K36 Methyltransferase Activity through Mrg15 Binding.,Hou P, Huang C, Liu CP, Yang N, Yu T, Yin Y, Zhu B, Xu RM Structure. 2019 Feb 12. pii: S0969-2126(19)30015-2. doi:, 10.1016/j.str.2019.01.015. PMID:30827843^[4]

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

References

↑ An S, Yeo KJ, Jeon YH, Song JJ. Crystal structure of the human histone methyltransferase ASH1L catalytic domain and its implications for the regulatory mechanism. J Biol Chem. 2011 Mar 11;286(10):8369-74. Epub 2011 Jan 14. PMID:21239497 doi:10.1074/jbc.M110.203380
↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
↑ Hayakawa T, Zhang F, Hayakawa N, Ohtani Y, Shinmyozu K, Nakayama J, Andreassen PR. MRG15 binds directly to PALB2 and stimulates homology-directed repair of chromosomal breaks. J Cell Sci. 2010 Apr 1;123(Pt 7):1124-30. doi: 10.1242/jcs.060178. PMID:20332121 doi:http://dx.doi.org/10.1242/jcs.060178
↑ Hou P, Huang C, Liu CP, Yang N, Yu T, Yin Y, Zhu B, Xu RM. Structural Insights into Stimulation of Ash1L's H3K36 Methyltransferase Activity through Mrg15 Binding. Structure. 2019 Feb 12. pii: S0969-2126(19)30015-2. doi:, 10.1016/j.str.2019.01.015. PMID:30827843 doi:http://dx.doi.org/10.1016/j.str.2019.01.015

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/6ine"

@@ Line 3: / Line 3: @@
 <StructureSection load='6ine' size='340' side='right'caption='[[6ine]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ine]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6INE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6INE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ine]] is a 2 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=6INE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6INE FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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">ASH1L, KIAA1420, KMT2H ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MORF4L1, MRG15, FWP006, HSPC008, HSPC061, PP368 ([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=6ine FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ine OCA], [http://pdbe.org/6ine PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ine RCSB], [http://www.ebi.ac.uk/pdbsum/6ine PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ine ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 </StructureSection>
 [[Category: Histone-lysine N-methyltransferase]]
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Hou, P]]

6ine

From Proteopedia

Revision as of 07:34, 23 May 2019

Crystal Structure of human ASH1L-MRG15 complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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