4l58

From Proteopedia

(Difference between revisions)

Revision as of 12:00, 5 August 2016

Crystal structure of the MLL5 PHD finger in complex with H3K4me3

Structural highlights

4l58 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:
NonStd Res:
Gene:	MLL5, KMT2E (HUMAN)
Activity:	Histone-lysine N-methyltransferase, with EC number 2.1.1.43
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MLL5_HUMAN] Histone methyltransferase that specifically mono- and dimethylates 'Lys-4' of histone H3 (H3K4me1 and H3K4me2). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation. Plays an essential role in retinoic-acid-induced granulopoiesis by acting as a coactivator of RAR-alpha (RARA) in target gene promoters. Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages. Required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells. Overexpression inhibits cell cycle progression, while knockdown induces cell cycle arrest at both the G1 and G2/M phases.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The human mixed-lineage leukemia 5 (MLL5) protein mediates hematopoietic cell homeostasis, cell cycle, and survival; however, the molecular basis underlying MLL5 activities remains unknown. Here, we show that MLL5 is recruited to gene-rich euchromatic regions via the interaction of its plant homeodomain finger with the histone mark H3K4me3. The 1.48-A resolution crystal structure of MLL5 plant homeodomain in complex with the H3K4me3 peptide reveals a noncanonical binding mechanism, whereby K4me3 is recognized through a single aromatic residue and an aspartate. The binding induces a unique His-Asp swapping rearrangement mediated by a C-terminal alpha-helix. Phosphorylation of H3T3 and H3T6 abrogates the association with H3K4me3 in vitro and in vivo, releasing MLL5 from chromatin in mitosis. This regulatory switch is conserved in the Drosophila ortholog of MLL5, UpSET, and suggests the developmental control for targeting of H3K4me3. Together, our findings provide first insights into the molecular basis for the recruitment, exclusion, and regulation of MLL5 at chromatin.

Molecular basis for chromatin binding and regulation of MLL5.,Ali M, Rincon-Arano H, Zhao W, Rothbart SB, Tong Q, Parkhurst SM, Strahl BD, Deng LW, Groudine M, Kutateladze TG Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11296-301. doi:, 10.1073/pnas.1310156110. Epub 2013 Jun 24. PMID:23798402^[4]

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

References

↑ Deng LW, Chiu I, Strominger JL. MLL 5 protein forms intranuclear foci, and overexpression inhibits cell cycle progression. Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):757-62. Epub 2004 Jan 12. PMID:14718661 doi:10.1073/pnas.2036345100
↑ Cheng F, Liu J, Zhou SH, Wang XN, Chew JF, Deng LW. RNA interference against mixed lineage leukemia 5 resulted in cell cycle arrest. Int J Biochem Cell Biol. 2008;40(11):2472-81. Epub 2008 May 15. PMID:18573682 doi:S1357-2725(08)00177-5
↑ Fujiki R, Chikanishi T, Hashiba W, Ito H, Takada I, Roeder RG, Kitagawa H, Kato S. GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis. Nature. 2009 May 21;459(7245):455-9. Epub 2009 Apr 19. PMID:19377461 doi:nature07954
↑ Ali M, Rincon-Arano H, Zhao W, Rothbart SB, Tong Q, Parkhurst SM, Strahl BD, Deng LW, Groudine M, Kutateladze TG. Molecular basis for chromatin binding and regulation of MLL5. Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11296-301. doi:, 10.1073/pnas.1310156110. Epub 2013 Jun 24. PMID:23798402 doi:10.1073/pnas.1310156110

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/4l58"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the MLL5 PHD finger in complex with H3K4me3==
 <StructureSection load='4l58' size='340' side='right' caption='[[4l58]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4l58]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L58 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L58 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4l58]] 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=4L58 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L58 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>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MLL5, KMT2E ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MLL5, KMT2E ([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=4l58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l58 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4l58 RCSB], [http://www.ebi.ac.uk/pdbsum/4l58 PDBsum]</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=4l58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l58 OCA], [http://pdbe.org/4l58 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4l58 RCSB], [http://www.ebi.ac.uk/pdbsum/4l58 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4l58 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4l58" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 27: / Line 29: @@
 </StructureSection>
 [[Category: Histone-lysine N-methyltransferase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Ali, M]]
 [[Category: Kutateladze, T G]]
 [[Category: Tong, Q]]
 [[Category: Transferase]]

4l58

From Proteopedia

Revision as of 12:00, 5 August 2016

Crystal structure of the MLL5 PHD finger in complex with H3K4me3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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