View source for 5ils


==Autoinhibited ETV1==
<StructureSection load='5ils' size='340' side='right'caption='[[5ils]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ils]] is a 1 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=5ILS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ILS 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]] 1.399&#8491;</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=5ils FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ils OCA], [https://pdbe.org/5ils PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ils RCSB], [https://www.ebi.ac.uk/pdbsum/5ils PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ils ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ETV1_HUMAN ETV1_HUMAN] Ewing sarcoma. 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=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving ETV1 is found in patients with Erwing sarcoma. Translocation t(7;22)(p22;q12) with EWSR1.
== Function ==
[https://www.uniprot.org/uniprot/ETV1_HUMAN ETV1_HUMAN] Transcriptional activator that binds to DNA sequences containing the consensus pentanucleotide 5'-CGGA[AT]-3'.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Autoinhibition enables spatial and temporal regulation of cellular processes by coupling protein activity to surrounding conditions, often via protein partnerships or signaling pathways. We report the molecular basis of DNA-binding autoinhibition of ETS transcription factors ETV1, ETV4 and ETV5, which are often overexpressed in prostate cancer. Inhibitory elements that cooperate to repress DNA binding were identified in regions N- and C-terminal of the ETS domain. Crystal structures of these three factors revealed an alpha-helix in the C-terminal inhibitory domain that packs against the ETS domain and perturbs the conformation of its DNA-recognition helix. Nuclear magnetic resonance spectroscopy demonstrated that the N-terminal inhibitory domain (NID) is intrinsically disordered, yet utilizes transient intramolecular interactions with the DNA-recognition helix of the ETS domain to mediate autoinhibition. Acetylation of selected lysines within the NID activates DNA binding. This investigation revealed a distinctive mechanism for DNA-binding autoinhibition in the ETV1/4/5 subfamily involving a network of intramolecular interactions not present in other ETS factors. These distinguishing inhibitory elements provide a platform through which cellular triggers, such as protein-protein interactions or post-translational modifications, may specifically regulate the function of these oncogenic proteins.

Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5.,Currie SL, Lau DKW, Doane JJ, Whitby FG, Okon M, McIntosh LP, Graves BJ Nucleic Acids Res. 2017 Mar 17;45(5):2223-2241. doi: 10.1093/nar/gkx068. PMID:28161714<ref>PMID:28161714</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ils" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Currie SL]]
[[Category: Whitby FG]]