5dag: Difference between revisions

Line 1:

'''~~Unreleased~~ structure'''

==Crystal structure of PZP domain of human AF10 protein==

== Structural highlights ==

<table><tr><td colspan='2'>[[5dag]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DAG FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dah|5dah]]</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=5dag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dag OCA], [http://pdbe.org/5dag PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dag RCSB], [http://www.ebi.ac.uk/pdbsum/5dag PDBsum]</span></td></tr>

</table>

== Disease ==

[[http://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN]] Precursor T-cell acute lymphoblastic leukemia. A chromosomal aberration involving MLLT10 is associated with acute leukemias. Translocation t(10;11)(p12;q23) with KMT2A/MLL1. The result is a rogue activator protein. A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.

== Function ==

[[http://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>

== 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.

The ~~entry 5dag is ON HOLD until Paper Publication~~

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>

~~Authors: Chen~~, S.~~, Patel, D.J~~.

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

~~Description~~: ~~Crystal structure of PZP domain of human AF10 protein~~

~~[[Category: Unreleased Structures]]~~

== References ==

~~[[Category: Patel, D.J]]~~

__TOC__

</StructureSection>

[[Category: Chen, S]]

[[Category: Patel, D J]]

[[Category: Epigenetic]]

[[Category: H3k27 recognition]]

[[Category: Histone tail reader]]

[[Category: Peptide binding protein]]

[[Category: Phd finger]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Crystal structure of PZP domain of human AF10 protein==
+<StructureSection load='5dag' size='340' side='right' caption='[[5dag]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5dag]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DAG FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dah|5dah]]</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=5dag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dag OCA], [http://pdbe.org/5dag PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dag RCSB], [http://www.ebi.ac.uk/pdbsum/5dag PDBsum]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN]] Precursor T-cell acute lymphoblastic leukemia. A chromosomal aberration involving MLLT10 is associated with acute leukemias. Translocation t(10;11)(p12;q23) with KMT2A/MLL1. The result is a rogue activator protein.  A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.
+== Function ==
+[[http://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.
-The entry 5dag is ON HOLD  until Paper Publication
+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>
-Authors: Chen, S., Patel, D.J.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Crystal structure of PZP domain of human AF10 protein
+<div class="pdbe-citations 5dag" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
-[[Category: Patel, D.J]]
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Chen, S]]
+[[Category: Patel, D J]]
+[[Category: Epigenetic]]
+[[Category: H3k27 recognition]]
+[[Category: Histone tail reader]]
+[[Category: Peptide binding protein]]
+[[Category: Phd finger]]