View source for 5e8i


==Crystal structure of the DNA binding domain of human transcription factor FLI1 in complex with a 10-mer DNA ACCGGAAGTG==
<StructureSection load='5e8i' size='340' side='right'caption='[[5e8i]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5e8i]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Endothia_gyrosa Endothia gyrosa] 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=5E8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E8I 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]] 3.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=5e8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e8i OCA], [https://pdbe.org/5e8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e8i RCSB], [https://www.ebi.ac.uk/pdbsum/5e8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e8i ProSAT]</span></td></tr>
</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 ==
FLI1 (Friend leukemia integration 1) is a metazoan transcription factor that is upregulated in a number of cancers. In addition, rearrangements of the fli1 gene cause sarcomas, leukemias, and lymphomas. These rearrangements encode oncogenic transcription factors, in which the DNA binding domain (DBD or ETS domain) of FLI1 on the C-terminal side is fused to a part of an another protein on the N-terminal side. Such abnormal cancer cell-specific fusions retain the DNA binding properties of FLI1 and acquire non-native protein-protein or protein-nucleic acid interactions of the substituted region. As a result, these fusions trigger oncogenic transcriptional reprogramming of the host cell. Interactions of FLI1 fusions with other proteins and with itself play a critical role in the oncogenic regulatory functions, and they are currently under intense scrutiny, mechanistically and as potential novel anticancer drug targets. We report elusive crystal structures of the FLI1 DBD, alone and in complex with cognate DNA containing a GGAA recognition sequence. Both structures reveal a previously unrecognized dimer of this domain, consistent with its dimerization in solution. The homodimerization interface is helix-swapped and dominated by hydrophobic interactions, including those between two interlocking Phe362 residues. A mutation of Phe362 to an alanine disrupted the propensity of this domain to dimerize without perturbing its structure or the DNA binding function, consistent with the structural observations. We propose that FLI1 DBD dimerization plays a role in transcriptional activation and repression by FLI1 and its fusions at promoters containing multiple FLI1 binding sites.

Structural Basis for Dimerization and DNA Binding of Transcription Factor FLI1.,Hou C, Tsodikov OV Biochemistry. 2015 Dec 10. PMID:26618620<ref>PMID:26618620</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5e8i" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Endothia gyrosa]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hou C]]
[[Category: Tsodikov OV]]