5dag
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5dag]] 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=5DAG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DAG FirstGlance]. <br> | <table><tr><td colspan='2'>[[5dag]] 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=5DAG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DAG FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.6Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5dag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dag OCA], [https://pdbe.org/5dag PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dag RCSB], [https://www.ebi.ac.uk/pdbsum/5dag PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dag 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=5dag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dag OCA], [https://pdbe.org/5dag PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dag RCSB], [https://www.ebi.ac.uk/pdbsum/5dag PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dag ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN] Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA.<ref>PMID:17868029</ref> | [https://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN] Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA.<ref>PMID:17868029</ref> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | AF10, a DOT1L cofactor, is required for H3K79 methylation and cooperates with DOT1L in leukemogenesis. However, the molecular mechanism by which AF10 regulates DOT1L-mediated H3K79 methylation is not clear. Here we report that AF10 contains a "reader" domain that couples unmodified H3K27 recognition to H3K79 methylation. An AF10 region consisting of a PHD finger-Zn knuckle-PHD finger (PZP) folds into a single module that recognizes amino acids 22-27 of H3, and this interaction is abrogated by H3K27 modification. Structural studies reveal that H3 binding triggers rearrangement of the PZP module to form an H3(22-27)-accommodating channel and that the unmodified H3K27 side chain is encased in a compact hydrogen-bond acceptor-lined cage. In cells, PZP recognition of H3 is required for H3K79 dimethylation, expression of DOT1L-target genes, and proliferation of DOT1L-addicted leukemic cells. Together, our results uncover a pivotal role for H3K27-via readout by the AF10 PZP domain-in regulating the cancer-associated enzyme DOT1L. | ||
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| - | The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate DOT1L-Mediated Methylation of H3K79.,Chen S, Yang Z, Wilkinson AW, Deshpande AJ, Sidoli S, Krajewski K, Strahl BD, Garcia BA, Armstrong SA, Patel DJ, Gozani O Mol Cell. 2015 Oct 15;60(2):319-27. doi: 10.1016/j.molcel.2015.08.019. Epub 2015 , Oct 1. PMID:26439302<ref>PMID:26439302</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 5dag" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Crystal structure of PZP domain of human AF10 protein
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