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| | <StructureSection load='6ofz' size='340' side='right'caption='[[6ofz]], [[Resolution|resolution]] 1.85Å' scene=''> | | <StructureSection load='6ofz' size='340' side='right'caption='[[6ofz]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ofz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OFZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OFZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ofz]] is a 1 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=6OFZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OFZ FirstGlance]. <br> |
| - | </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=6ofz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofz OCA], [http://pdbe.org/6ofz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ofz RCSB], [http://www.ebi.ac.uk/pdbsum/6ofz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofz ProSAT]</span></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]] 1.85Å</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=6ofz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ofz OCA], [https://pdbe.org/6ofz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ofz RCSB], [https://www.ebi.ac.uk/pdbsum/6ofz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ofz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == 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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6ofz" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6ofz" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[WD-repeat protein 3D structures|WD-repeat protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Almo, S C]] | + | [[Category: Almo SC]] |
| - | [[Category: Bonanno, J B]] | + | [[Category: Bonanno JB]] |
| - | [[Category: Burgos, E]] | + | [[Category: Burgos E]] |
| - | [[Category: Harijan, R K]] | + | [[Category: Harijan RK]] |
| - | [[Category: Lorton, B M]] | + | [[Category: Lorton BM]] |
| - | [[Category: Shechter, D]] | + | [[Category: Shechter D]] |
| - | [[Category: Chromatin]]
| + | |
| - | [[Category: Epigenetic]]
| + | |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Methylarginine]]
| + | |
| - | [[Category: Methylation]]
| + | |
| - | [[Category: Post-translational modification]]
| + | |
| 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]
Publication Abstract from PubMed
Histone H3 arginine 2 (H3R2) is post-translationally modified in three different states by "writers" of the protein arginine methyltransferase (PRMT) family. H3R2 methylarginine isoforms include PRMT5-catalyzed monomethylation (me1) and symmetric dimethylation (me2s), and PRMT6-catalyzed me1 and asymmetric dimethylation (me2a). WD-40 repeat-containing protein 5 (WDR5) is an epigenetic "reader" protein that interacts with H3R2. Previous studies suggested that H3R2me2s specified a high-affinity interaction with WDR5. However, our prior biological data prompted the hypothesis that WDR5 may also interact with H3R2me1. Here, using highly accurate quantitative binding analysis combined with high-resolution crystal structures of WDR5 in complex with unmodified (me0) and me1/me2s L-Arginine amino acids and in complex with H3R2me1 peptide, we provide a rigorous biochemical study and address long-standing discrepancies of this important biological interaction. Despite modest structural differences at the binding interface, our study supports an interaction model regulated by a binary arginine methylation switch: H3R2me2a prevents interaction with WDR5, whereas H3R2me0/me1/me2s are equally permissive.
A binary arginine methylation switch on histone H3 Arginine 2 regulates its interaction with WDR5.,Lorton BM, Harijan RK, Burgos ES, Bonanno JB, Almo SC, Shechter D Biochemistry. 2020 Mar 24. doi: 10.1021/acs.biochem.0c00035. PMID:32207970[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
- ↑ Lorton BM, Harijan RK, Burgos ES, Bonanno JB, Almo SC, Shechter D. A binary arginine methylation switch on histone H3 Arginine 2 regulates its interaction with WDR5. Biochemistry. 2020 Mar 24. doi: 10.1021/acs.biochem.0c00035. PMID:32207970 doi:http://dx.doi.org/10.1021/acs.biochem.0c00035
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