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| | ==Crystal structure of Ash2L SPRY domain in complex with phosphorylated RbBP5== | | ==Crystal structure of Ash2L SPRY domain in complex with phosphorylated RbBP5== |
| - | <StructureSection load='4x8n' size='340' side='right' caption='[[4x8n]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='4x8n' size='340' side='right'caption='[[4x8n]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4x8n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X8N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X8N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4x8n]] 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=4X8N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X8N FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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">[[4x8p|4x8p]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=4x8n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x8n OCA], [http://pdbe.org/4x8n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x8n RCSB], [http://www.ebi.ac.uk/pdbsum/4x8n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x8n 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=4x8n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x8n OCA], [https://pdbe.org/4x8n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x8n RCSB], [https://www.ebi.ac.uk/pdbsum/4x8n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x8n ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ASH2L_HUMAN ASH2L_HUMAN]] Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. May function as a transcriptional regulator. May play a role in hematopoiesis.<ref>PMID:12670868</ref> <ref>PMID:19556245</ref> [[http://www.uniprot.org/uniprot/RBBP5_HUMAN RBBP5_HUMAN]] In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (By similarity). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3. Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation.<ref>PMID:19556245</ref> | + | [https://www.uniprot.org/uniprot/ASH2L_HUMAN ASH2L_HUMAN] Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. May function as a transcriptional regulator. May play a role in hematopoiesis.<ref>PMID:12670868</ref> <ref>PMID:19556245</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 4x8n" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4x8n" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brand, M]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Brunzelle, J S]] | + | [[Category: Large Structures]] |
| - | [[Category: Chaturvedi, C P]] | + | [[Category: Brand M]] |
| - | [[Category: Couture, J F]] | + | [[Category: Brunzelle JS]] |
| - | [[Category: Shilatifard, A]] | + | [[Category: Chaturvedi CP]] |
| - | [[Category: Skiniotis, G]] | + | [[Category: Couture J-F]] |
| - | [[Category: Zhang, P]] | + | [[Category: Shilatifard A]] |
| - | [[Category: Chromatin]] | + | [[Category: Skiniotis G]] |
| - | [[Category: Epigenetic]] | + | [[Category: Zhang P]] |
| - | [[Category: Histone]]
| + | |
| - | [[Category: Mll1]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
ASH2L_HUMAN Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. May function as a transcriptional regulator. May play a role in hematopoiesis.[1] [2]
Publication Abstract from PubMed
The methyltransferase activity of the trithorax group (TrxG) protein MLL1 found within its COMPASS (complex associated with SET1)-like complex is allosterically regulated by a four-subunit complex composed of WDR5, RbBP5, Ash2L, and DPY30 (also referred to as WRAD). We report structural evidence showing that in WRAD, a concave surface of the Ash2L SPIa and ryanodine receptor (SPRY) domain binds to a cluster of acidic residues, referred to as the D/E box, in RbBP5. Mutational analysis shows that residues forming the Ash2L/RbBP5 interface are important for heterodimer formation, stimulation of MLL1 catalytic activity, and erythroid cell terminal differentiation. We also demonstrate that a phosphorylation switch on RbBP5 stimulates WRAD complex formation and significantly increases KMT2 (lysine [K] methyltransferase 2) enzyme methylation rates. Overall, our findings provide structural insights into the assembly of the WRAD complex and point to a novel regulatory mechanism controlling the activity of the KMT2/COMPASS family of lysine methyltransferases.
A phosphorylation switch on RbBP5 regulates histone H3 Lys4 methylation.,Zhang P, Chaturvedi CP, Tremblay V, Cramet M, Brunzelle JS, Skiniotis G, Brand M, Shilatifard A, Couture JF Genes Dev. 2015 Jan 15;29(2):123-8. doi: 10.1101/gad.254870.114. PMID:25593305[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wysocka J, Myers MP, Laherty CD, Eisenman RN, Herr W. Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes Dev. 2003 Apr 1;17(7):896-911. PMID:12670868 doi:10.1101/gad.252103
- ↑ 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
- ↑ Zhang P, Chaturvedi CP, Tremblay V, Cramet M, Brunzelle JS, Skiniotis G, Brand M, Shilatifard A, Couture JF. A phosphorylation switch on RbBP5 regulates histone H3 Lys4 methylation. Genes Dev. 2015 Jan 15;29(2):123-8. doi: 10.1101/gad.254870.114. PMID:25593305 doi:http://dx.doi.org/10.1101/gad.254870.114
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