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| | <StructureSection load='2cnx' size='340' side='right'caption='[[2cnx]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='2cnx' size='340' side='right'caption='[[2cnx]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2cnx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CNX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2cnx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CNX FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2co0|2co0]], [[2gnq|2gnq]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></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=2cnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cnx OCA], [https://pdbe.org/2cnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cnx RCSB], [https://www.ebi.ac.uk/pdbsum/2cnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cnx ProSAT]</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=2cnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cnx OCA], [https://pdbe.org/2cnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cnx RCSB], [https://www.ebi.ac.uk/pdbsum/2cnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cnx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN]] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref>
| + | [https://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allis, C D]] | + | [[Category: Allis CD]] |
| - | [[Category: Graybosch, D M]] | + | [[Category: Graybosch DM]] |
| - | [[Category: Li, H]] | + | [[Category: Li H]] |
| - | [[Category: Patel, D J]] | + | [[Category: Patel DJ]] |
| - | [[Category: Ruthenburg, A J]] | + | [[Category: Ruthenburg AJ]] |
| - | [[Category: Verdine, G L]] | + | [[Category: Verdine GL]] |
| - | [[Category: Wang, W]] | + | [[Category: Wang W]] |
| - | [[Category: Histone presenter]]
| + | |
| - | [[Category: Hox gene activation]]
| + | |
| - | [[Category: Leukemia]]
| + | |
| - | [[Category: Lysine methylation]]
| + | |
| - | [[Category: Mll1]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription activation]]
| + | |
| Structural highlights
Function
WDR5_HUMAN Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
WDR5 is a core component of SET1-family complexes that achieve transcriptional activation via methylation of histone H3 on Nzeta of Lys4 (H3K4). The role of WDR5 in the MLL1 complex has recently been described as specific recognition of dimethyl-K4 in the context of a histone H3 amino terminus; WDR5 is essential for vertebrate development, Hox gene activation and global H3K4 trimethylation. We report the high-resolution X-ray structures of WDR5 in the unliganded form and complexed with histone H3 peptides having unmodified and mono-, di- and trimethylated K4, which together provide the first comprehensive analysis of methylated histone recognition by the ubiquitous WD40-repeat fold. Contrary to predictions, the structures reveal that WDR5 does not read out the methylation state of K4 directly, but instead serves to present the K4 side chain for further methylation by SET1-family complexes.
Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex.,Ruthenburg AJ, Wang W, Graybosch DM, Li H, Allis CD, Patel DJ, Verdine GL Nat Struct Mol Biol. 2006 Aug;13(8):704-12. Epub 2006 Jul 9. PMID:16829959[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Patel A, Dharmarajan V, Vought VE, Cosgrove MS. On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex. J Biol Chem. 2009 Sep 4;284(36):24242-56. Epub 2009 Jun 25. PMID:19556245 doi:M109.014498
- ↑ Guelman S, Kozuka K, Mao Y, Pham V, Solloway MJ, Wang J, Wu J, Lill JR, Zha J. The double-histone-acetyltransferase complex ATAC is essential for mammalian development. Mol Cell Biol. 2009 Mar;29(5):1176-88. doi: 10.1128/MCB.01599-08. Epub 2008 Dec, 22. PMID:19103755 doi:10.1128/MCB.01599-08
- ↑ Cai Y, Jin J, Swanson SK, Cole MD, Choi SH, Florens L, Washburn MP, Conaway JW, Conaway RC. Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex. J Biol Chem. 2010 Feb 12;285(7):4268-72. doi: 10.1074/jbc.C109.087981. Epub 2009 , Dec 14. PMID:20018852 doi:10.1074/jbc.C109.087981
- ↑ Han Z, Guo L, Wang H, Shen Y, Deng XW, Chai J. Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. Mol Cell. 2006 Apr 7;22(1):137-44. PMID:16600877 doi:10.1016/j.molcel.2006.03.018
- ↑ Couture JF, Collazo E, Trievel RC. Molecular recognition of histone H3 by the WD40 protein WDR5. Nat Struct Mol Biol. 2006 Aug;13(8):698-703. Epub 2006 Jul 9. PMID:16829960 doi:10.1038/nsmb1116
- ↑ Ruthenburg AJ, Wang W, Graybosch DM, Li H, Allis CD, Patel DJ, Verdine GL. Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex. Nat Struct Mol Biol. 2006 Aug;13(8):704-12. Epub 2006 Jul 9. PMID:16829959 doi:10.1038/nsmb1119
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