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| | ==PHF1 Tudor in complex with H3K36me3== | | ==PHF1 Tudor in complex with H3K36me3== |
| - | <StructureSection load='4hcz' size='340' side='right' caption='[[4hcz]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='4hcz' size='340' side='right'caption='[[4hcz]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hcz]] is a 4 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=4HCZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HCZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hcz]] is a 4 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=4HCZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HCZ FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PHF1, PCL1 ([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=4hcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hcz OCA], [https://pdbe.org/4hcz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hcz RCSB], [https://www.ebi.ac.uk/pdbsum/4hcz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hcz ProSAT]</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=4hcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hcz OCA], [http://pdbe.org/4hcz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hcz RCSB], [http://www.ebi.ac.uk/pdbsum/4hcz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hcz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PHF1_HUMAN PHF1_HUMAN]] Transcriptional repressor. May promote methylation of histone H3 on 'Lys-27' by the PRC2/EED-EZH2 complex.<ref>PMID:18086877</ref> <ref>PMID:18285464</ref> | + | [https://www.uniprot.org/uniprot/PHF1_HUMAN PHF1_HUMAN] Transcriptional repressor. May promote methylation of histone H3 on 'Lys-27' by the PRC2/EED-EZH2 complex.<ref>PMID:18086877</ref> <ref>PMID:18285464</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Kutateladze, T G]] | + | [[Category: Large Structures]] |
| - | [[Category: Musselman, C A]] | + | [[Category: Kutateladze TG]] |
| - | [[Category: Nunez, J]] | + | [[Category: Musselman CA]] |
| - | [[Category: Roy, S]] | + | [[Category: Nunez J]] |
| - | [[Category: H3k36me3]] | + | [[Category: Roy S]] |
| - | [[Category: Histone binding]]
| + | |
| - | [[Category: Na]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Protein-peptide complex]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Tudor]]
| + | |
| Structural highlights
Function
PHF1_HUMAN Transcriptional repressor. May promote methylation of histone H3 on 'Lys-27' by the PRC2/EED-EZH2 complex.[1] [2]
Publication Abstract from PubMed
The PHD finger protein 1 (PHF1) is essential in epigenetic regulation and genome maintenance. Here we show that the Tudor domain of human PHF1 binds to histone H3 trimethylated at Lys36 (H3K36me3). We report a 1.9-A resolution crystal structure of the Tudor domain in complex with H3K36me3 and describe the molecular mechanism of H3K36me3 recognition using NMR. Binding of PHF1 to H3K36me3 inhibits the ability of the Polycomb PRC2 complex to methylate Lys27 of histone H3 in vitro and in vivo. Laser microirradiation data show that PHF1 is transiently recruited to DNA double-strand breaks, and PHF1 mutants impaired in the H3K36me3 interaction exhibit reduced retention at double-strand break sites. Together, our findings suggest that PHF1 can mediate deposition of the repressive H3K27me3 mark and acts as a cofactor in early DNA-damage response.
Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1.,Musselman CA, Avvakumov N, Watanabe R, Abraham CG, Lalonde ME, Hong Z, Allen C, Roy S, Nunez JK, Nickoloff J, Kulesza CA, Yasui A, Cote J, Kutateladze TG Nat Struct Mol Biol. 2012 Dec;19(12):1266-72. doi: 10.1038/nsmb.2435. Epub 2012, Nov 11. PMID:23142980[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cao R, Wang H, He J, Erdjument-Bromage H, Tempst P, Zhang Y. Role of hPHF1 in H3K27 methylation and Hox gene silencing. Mol Cell Biol. 2008 Mar;28(5):1862-72. Epub 2007 Dec 17. PMID:18086877 doi:http://dx.doi.org/10.1128/MCB.01589-07
- ↑ Sarma K, Margueron R, Ivanov A, Pirrotta V, Reinberg D. Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo. Mol Cell Biol. 2008 Apr;28(8):2718-31. doi: 10.1128/MCB.02017-07. Epub 2008 Feb, 19. PMID:18285464 doi:10.1128/MCB.02017-07
- ↑ Musselman CA, Avvakumov N, Watanabe R, Abraham CG, Lalonde ME, Hong Z, Allen C, Roy S, Nunez JK, Nickoloff J, Kulesza CA, Yasui A, Cote J, Kutateladze TG. Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1. Nat Struct Mol Biol. 2012 Dec;19(12):1266-72. doi: 10.1038/nsmb.2435. Epub 2012, Nov 11. PMID:23142980 doi:http://dx.doi.org/10.1038/nsmb.2435
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