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==== | ==Crystal structure of the DNA binding domain of human transcription factor FLI1 in complex with 16-mer DNA CAGAGGATGTGGCTTC== | ||
<StructureSection load='6vg2' size='340' side='right'caption='[[6vg2]]' scene=''> | <StructureSection load='6vg2' size='340' side='right'caption='[[6vg2]], [[Resolution|resolution]] 3.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6vg2]] is a 6 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=6VG2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VG2 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.9Å</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=6vg2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vg2 OCA], [https://pdbe.org/6vg2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vg2 RCSB], [https://www.ebi.ac.uk/pdbsum/6vg2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vg2 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[https://www.uniprot.org/uniprot/FLI1_HUMAN FLI1_HUMAN] Defects in FLI1 are a cause of Ewing sarcoma (ES) [MIM:[https://omim.org/entry/612219 612219]. A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. Note=A chromosomal aberration involving FLI1 is found in patients with Erwing sarcoma. Translocation t(11;22)(q24;q12) with EWSR1. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FLI1_HUMAN FLI1_HUMAN] Sequence-specific transcriptional activator. Recognizes the DNA sequence 5'-C[CA]GGAAGT-3'. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
ETS family transcription factors of ERG and FLI1 play a key role in oncogenesis of prostate cancer and Ewing sarcoma by binding regulatory DNA sites and interfering with function of other factors. Mithramycin (MTM) is an anti-cancer, DNA binding natural product that functions as a potent antagonist of ERG and FLI1 by an unknown mechanism. We present a series of crystal structures of the DNA binding domain (DBD) of ERG/FLI1 culminating in a structure of a high-order complex of the ERG/FLI1 DBD, transcription factor Runx2, core-binding factor beta (Cbfbeta), and MTM on a DNA enhancer site, along with supporting DNA binding studies using MTM and its analogues. Taken together, these data provide insight into allosteric mechanisms underlying ERG and FLI1 transactions and their disruption by MTM analogues. | |||
Allosteric interference in oncogenic FLI1 and ERG transactions by mithramycins.,Hou C, Mandal A, Rohr J, Tsodikov OV Structure. 2021 May 6;29(5):404-412.e4. doi: 10.1016/j.str.2020.11.012. Epub 2020 , Dec 3. PMID:33275876<ref>PMID:33275876</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6vg2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Core-binding factor|Core-binding factor]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Hou C]] | ||
[[Category: Tsodikov OV]] |