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| | ==Crystal structure of WDR5 in complex with the WDR5-interacting motif of MLL2== | | ==Crystal structure of WDR5 in complex with the WDR5-interacting motif of MLL2== |
| - | <StructureSection load='3uvk' size='340' side='right' caption='[[3uvk]], [[Resolution|resolution]] 1.40Å' scene=''> | + | <StructureSection load='3uvk' size='340' side='right'caption='[[3uvk]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3uvk]] 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=3UVK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UVK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3uvk]] 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=3UVK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UVK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3uvl|3uvl]], [[3uvm|3uvm]], [[3uvn|3uvn]], [[3uvo|3uvo]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WDR5, BIG3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3uvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uvk OCA], [https://pdbe.org/3uvk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uvk RCSB], [https://www.ebi.ac.uk/pdbsum/3uvk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uvk ProSAT]</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-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>
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| - | <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=3uvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uvk OCA], [http://pdbe.org/3uvk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3uvk RCSB], [http://www.ebi.ac.uk/pdbsum/3uvk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3uvk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/KMT2D_HUMAN KMT2D_HUMAN]] Kabuki syndrome. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/KMT2D_HUMAN KMT2D_HUMAN]] Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription.<ref>PMID:16603732</ref> <ref>PMID:17500065</ref> <ref>PMID:17851529</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> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | In mammals, the SET1 family of lysine methyltransferases (KMTs), which includes MLL1-5, SET1A and SET1B, catalyzes the methylation of lysine-4 (Lys-4) on histone H3. Recent reports have demonstrated that a three-subunit complex composed of WD-repeat protein-5 (WDR5), retinoblastoma-binding protein-5 (RbBP5) and absent, small, homeotic disks-2-like (ASH2L) stimulates the methyltransferase activity of MLL1. On the basis of studies showing that this stimulation is in part controlled by an interaction between WDR5 and a small region located in close proximity of the MLL1 catalytic domain [referred to as the WDR5-interacting motif (Win)], it has been suggested that WDR5 might play an analogous role in scaffolding the other SET1 complexes. We herein provide biochemical and structural evidence showing that WDR5 binds the Win motifs of MLL2-4, SET1A and SET1B. Comparative analysis of WDR5-Win complexes reveals that binding of the Win motifs is achieved by the plasticity of WDR5 peptidyl-arginine-binding cleft allowing the C-terminal ends of the Win motifs to be maintained in structurally divergent conformations. Consistently, enzymatic assays reveal that WDR5 plays an important role in the optimal stimulation of MLL2-4, SET1A and SET1B methyltransferase activity by the RbBP5-ASH2L heterodimer. Overall, our findings illustrate the function of WDR5 in scaffolding the SET1 family of KMTs and further emphasize on the important role of WDR5 in regulating global histone H3 Lys-4 methylation.
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| - | The plasticity of WDR5 peptide-binding cleft enables the binding of the SET1 family of histone methyltransferases.,Zhang P, Lee H, Brunzelle JS, Couture JF Nucleic Acids Res. 2012 Jan 20. PMID:22266653<ref>PMID:22266653</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3uvk" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
| - | *[[WD-repeat protein 5|WD-repeat protein 5]] | + | *[[WD-repeat protein 3D structures|WD-repeat protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Histone-lysine N-methyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Brunzelle, J S]] | + | [[Category: Brunzelle JS]] |
| - | [[Category: Couture, J F]] | + | [[Category: Couture J-F]] |
| - | [[Category: Lee, H]] | + | [[Category: Lee H]] |
| - | [[Category: Zhang, P]] | + | [[Category: Zhang P]] |
| - | [[Category: Beta-propeller]]
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| - | [[Category: Chromatin biology]]
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| - | [[Category: Histone h3]]
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| - | [[Category: Nucleus]]
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| - | [[Category: Scaffolding]]
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| - | [[Category: Transcription]]
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| - | [[Category: Trithorax]]
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