6cko: Difference between revisions
New page: '''Unreleased structure''' The entry 6cko is ON HOLD Authors: Zhang, H., Tempel, W., Bountra, C., Arrowsmith, C.H., Edwards, A.M., Min, J., Structural Genomics Consortium (SGC) Descrip... |
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The | ==Crystal structure of an AF10 fragment== | ||
<StructureSection load='6cko' size='340' side='right'caption='[[6cko]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6cko]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CKO FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</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=6cko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cko OCA], [https://pdbe.org/6cko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cko RCSB], [https://www.ebi.ac.uk/pdbsum/6cko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cko ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://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 == | |||
[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 == | |||
The mixed-lineage leukemia (MLL)-AF10 fusion oncoprotein recruits DOT1L to the homeobox A (HOXA) gene cluster through its octapeptide motif leucine zipper (OM-LZ), thereby inducing and maintaining the MLL-AF10-associated leukemogenesis. However, the recognition mechanism between DOT1L and MLL-AF10 is unclear. Here, we present the crystal structures of both apo AF10(OM-LZ) and its complex with the coiled-coil domain of DOT1L. Disruption of the DOT1L-AF10 interface abrogates MLL-AF10-associated leukemic transformation. We further show that zinc stabilizes the DOT1L-AF10 complex and may be involved in the regulation of the HOXA gene expression. Our studies may also pave the way for the rational design of therapeutic drugs against MLL-rearranged leukemia. | |||
Structural and functional analysis of the DOT1L-AF10 complex reveals mechanistic insights into MLL-AF10-associated leukemogenesis.,Zhang H, Zhou B, Qin S, Xu J, Harding R, Tempel W, Nayak V, Li Y, Loppnau P, Dou Y, Min J Genes Dev. 2018 Mar 1;32(5-6):341-346. doi: 10.1101/gad.311639.118. Epub 2018 Mar, 21. PMID:29563185<ref>PMID:29563185</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6cko" style="background-color:#fffaf0;"></div> | ||
[[Category: Arrowsmith | |||
[[Category: | ==See Also== | ||
[[Category: Edwards | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Danio rerio]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Arrowsmith CH]] | |||
[[Category: Bountra C]] | |||
[[Category: Edwards AM]] | |||
[[Category: Min J]] | |||
[[Category: Tempel W]] | |||
[[Category: Zhang H]] | |||