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| | ==Crystal structure of Runx1 and Ets1 bound to TCR alpha promoter (crystal form 1)== | | ==Crystal structure of Runx1 and Ets1 bound to TCR alpha promoter (crystal form 1)== |
| - | <StructureSection load='4l0y' size='340' side='right' caption='[[4l0y]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4l0y' size='340' side='right'caption='[[4l0y]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4l0y]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L0Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L0Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4l0y]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L0Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L0Y FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4l0z|4l0z]], [[4l18|4l18]]</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]] 2.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Runx1, Aml1, Cbfa2, Pebp2ab ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), ETS1, EWSR2 ([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=4l0y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l0y OCA], [https://pdbe.org/4l0y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l0y RCSB], [https://www.ebi.ac.uk/pdbsum/4l0y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l0y 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=4l0y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l0y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4l0y RCSB], [http://www.ebi.ac.uk/pdbsum/4l0y PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/RUNX1_MOUSE RUNX1_MOUSE]] Note=Mice with an Runx1 lacking the DNA-binding region are found to die between embryonic days 11.5 to 12.5 due to hemorrhaging in the central nervous system. This hemorrhaging is preceded by necrosis and hematopoiesis is blocked. | + | [https://www.uniprot.org/uniprot/RUNX1_MOUSE RUNX1_MOUSE] Note=Mice with an Runx1 lacking the DNA-binding region are found to die between embryonic days 11.5 to 12.5 due to hemorrhaging in the central nervous system. This hemorrhaging is preceded by necrosis and hematopoiesis is blocked. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RUNX1_MOUSE RUNX1_MOUSE]] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. Essential for the development of normal hematopoiesis. Isoform 4 shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter. Inhibits KAT6B-dependent transcriptional activation (By similarity).<ref>PMID:8565077</ref> <ref>PMID:8622955</ref> [[http://www.uniprot.org/uniprot/ETS1_HUMAN ETS1_HUMAN]] Transcription factor.<ref>PMID:10698492</ref> | + | [https://www.uniprot.org/uniprot/RUNX1_MOUSE RUNX1_MOUSE] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. Essential for the development of normal hematopoiesis. Isoform 4 shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter. Inhibits KAT6B-dependent transcriptional activation (By similarity).<ref>PMID:8565077</ref> <ref>PMID:8622955</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Runx1 is required for definitive hematopoiesis and is well-known for its frequent chromosomal translocations and point mutations in leukemia. Runx1 regulates a variety of genes via Ets1 activation on an Ets1*Runx1 composite DNA sequence. The structural basis of such regulation remains unresolved. To address this problem, we determined the crystal structure of the ternary complex containing Runx11-242 and Ets1296-441 bound to T cell receptor alpha (TCRalpha) enhancer DNA. In the crystal, an Ets1-interacting domain of Runx1 is bound to the Ets1 DNA-binding domain and displaced an entire autoinhibitory module of Ets1, revealing a novel mechanism of Ets1 activation. The DNA binding and transcriptional studies with a variety of structure-guided Runx1 mutants confirmed a critical role of direct Ets1*Runx1 interaction in Ets1 activation. More importantly, the discovered mechanism provides a plausible explanation for how the Ets1*Runx1 interaction effectively activates not only a wild-type Ets1, but also a highly inhibited phosphorylated form of Ets1.Leukemia accepted article preview online, 20 March 2014; doi:10.1038/leu.2014.111.
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| - | Structural basis of Ets1 activation by Runx1.,Shrivastava T, Mino K, Babayeva ND, Baranovskaya OI, Rizzino A, Tahirov TH Leukemia. 2014 Mar 20. doi: 10.1038/leu.2014.111. PMID:24646888<ref>PMID:24646888</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | ==See Also== | | ==See Also== |
| | + | *[[Core-binding factor|Core-binding factor]] |
| | *[[Ets1|Ets1]] | | *[[Ets1|Ets1]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Tahirov, T H]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ets domain]] | + | [[Category: Tahirov TH]] |
| - | [[Category: Runt domain]]
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| - | [[Category: Transcription-dna complex]]
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