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| | ==Autoinhibited ETV4== | | ==Autoinhibited ETV4== |
| - | <StructureSection load='5ilu' size='340' side='right' caption='[[5ilu]], [[Resolution|resolution]] 1.10Å' scene=''> | + | <StructureSection load='5ilu' size='340' side='right'caption='[[5ilu]], [[Resolution|resolution]] 1.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ilu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ILU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ILU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ilu]] 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=5ILU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ILU FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ils|5ils]], [[5ilv|5ilv]]</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]] 1.101Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ETV4, E1AF, PEA3 ([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=5ilu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ilu OCA], [https://pdbe.org/5ilu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ilu RCSB], [https://www.ebi.ac.uk/pdbsum/5ilu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ilu 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=5ilu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ilu OCA], [http://pdbe.org/5ilu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ilu RCSB], [http://www.ebi.ac.uk/pdbsum/5ilu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ilu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ETV4_HUMAN ETV4_HUMAN]] Ewing sarcoma. | + | [https://www.uniprot.org/uniprot/ETV4_HUMAN ETV4_HUMAN] Ewing sarcoma. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ETV4_HUMAN ETV4_HUMAN]] Transcriptional activator that binds to the enhancer of the adenovirus E1A gene; the core-binding sequence is 5'[AC]GGA[AT]GT-3'.<ref>PMID:19307308</ref> | + | [https://www.uniprot.org/uniprot/ETV4_HUMAN ETV4_HUMAN] Transcriptional activator that binds to the enhancer of the adenovirus E1A gene; the core-binding sequence is 5'[AC]GGA[AT]GT-3'.<ref>PMID:19307308</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Currie, S L]] | + | [[Category: Large Structures]] |
| - | [[Category: Whitby, F G]] | + | [[Category: Currie SL]] |
| - | [[Category: Autoinhibition transcription]] | + | [[Category: Whitby FG]] |
| - | [[Category: Dna binding]]
| + | |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Et]]
| + | |
| - | [[Category: Etv4]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| Structural highlights
Disease
ETV4_HUMAN Ewing sarcoma.
Function
ETV4_HUMAN Transcriptional activator that binds to the enhancer of the adenovirus E1A gene; the core-binding sequence is 5'[AC]GGA[AT]GT-3'.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Guo B, Sharrocks AD. Extracellular signal-regulated kinase mitogen-activated protein kinase signaling initiates a dynamic interplay between sumoylation and ubiquitination to regulate the activity of the transcriptional activator PEA3. Mol Cell Biol. 2009 Jun;29(11):3204-18. doi: 10.1128/MCB.01128-08. Epub 2009 Mar , 23. PMID:19307308 doi:http://dx.doi.org/10.1128/MCB.01128-08
- ↑ Currie SL, Lau DKW, Doane JJ, Whitby FG, Okon M, McIntosh LP, Graves BJ. Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5. Nucleic Acids Res. 2017 Mar 17;45(5):2223-2241. doi: 10.1093/nar/gkx068. PMID:28161714 doi:http://dx.doi.org/10.1093/nar/gkx068
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