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| | <StructureSection load='3zp5' size='340' side='right'caption='[[3zp5]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='3zp5' size='340' side='right'caption='[[3zp5]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zp5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZP5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zp5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZP5 FirstGlance]. <br> |
| - | </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=3zp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zp5 OCA], [https://pdbe.org/3zp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zp5 RCSB], [https://www.ebi.ac.uk/pdbsum/3zp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zp5 ProSAT]</span></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]] 2Å</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=3zp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zp5 OCA], [https://pdbe.org/3zp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zp5 RCSB], [https://www.ebi.ac.uk/pdbsum/3zp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zp5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/FEV_HUMAN FEV_HUMAN]] Disease susceptibility may be associated with variations affecting the gene represented in this entry. A chromosomal aberration involving FEV is found in Ewing tumors. Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with a potential oncogenic activity.
| + | [https://www.uniprot.org/uniprot/FEV_HUMAN FEV_HUMAN] Disease susceptibility may be associated with variations affecting the gene represented in this entry. A chromosomal aberration involving FEV is found in Ewing tumors. Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with a potential oncogenic activity. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/FEV_HUMAN FEV_HUMAN]] Functions as a transcriptional regulator. According to PubMed:12761502, it functions as a transcriptional repressor. Functions in the differentiation and the maintenance of the central serotonergic neurons. May play a role in cell growth.<ref>PMID:12761502</ref>
| + | [https://www.uniprot.org/uniprot/FEV_HUMAN FEV_HUMAN] Functions as a transcriptional regulator. According to PubMed:12761502, it functions as a transcriptional repressor. Functions in the differentiation and the maintenance of the central serotonergic neurons. May play a role in cell growth.<ref>PMID:12761502</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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allerston, C K]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Allerston CK]] |
| - | [[Category: Burgess-Brown, N]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Cooper, C D.O]] | + | [[Category: Burgess-Brown N]] |
| - | [[Category: Delft, F von]]
| + | [[Category: Cooper CDO]] |
| - | [[Category: Edwards, A]] | + | [[Category: Edwards A]] |
| - | [[Category: Gileadi, O]] | + | [[Category: Gileadi O]] |
| - | [[Category: Krojer, T]] | + | [[Category: Krojer T]] |
| - | [[Category: Newman, J A]] | + | [[Category: Newman JA]] |
| - | [[Category: Shrestha, L]] | + | [[Category: Shrestha L]] |
| - | [[Category: Vollmar, M]] | + | [[Category: Vollmar M]] |
| - | [[Category: Transcription-dna complex]] | + | [[Category: Von Delft F]] |
| Structural highlights
Disease
FEV_HUMAN Disease susceptibility may be associated with variations affecting the gene represented in this entry. A chromosomal aberration involving FEV is found in Ewing tumors. Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with a potential oncogenic activity.
Function
FEV_HUMAN Functions as a transcriptional regulator. According to PubMed:12761502, it functions as a transcriptional repressor. Functions in the differentiation and the maintenance of the central serotonergic neurons. May play a role in cell growth.[1]
Publication Abstract from PubMed
Ets transcription factors, which share the conserved Ets DNA-binding domain, number nearly 30 members in humans and are particularly involved in developmental processes. Their deregulation following changes in expression, transcriptional activity, or by chromosomal translocation, plays a critical role in carcinogenesis. Ets DNA-binding, selectivity and regulation have been extensively studied, although questions still arise regarding binding specificity outside the core GGA recognition sequence, and the mode of action of Ets post-translational modifications. Here we report the crystal structures of ETV1, ETV4, ETV5 and FEV, alone and in complex with DNA. We identify previously unrecognized features of the protein-DNA interface. Interactions with the DNA backbone account for most of the binding affinity. We describe a highly coordinated network of water molecules acting in base selection upstream of the GGAA core, and the structural features that may account for discrimination against methylated cytidine residues. Unexpectedly, all proteins crystallized as disulfide-linked dimers, exhibiting a novel interface (distant to the DNA recognition helix). Homodimers of ETV1, ETV4 and ETV5 could be reduced to monomers, leading to a 40-200-fold increase in DNA binding affinity. Hence, we present the first indication of a redox-dependent regulatory mechanism which may control the activity of this subset of oncogenic Ets transcription factors.
Structures of the Ets Domains of Transcription Factors ETV1, ETV4, ETV5 and FEV: Determinants of DNA Binding and Redox Regulation by Disulfide bond formation.,Cooper CD, Newman JA, Aitkenhead H, Allerston CK, Gileadi O J Biol Chem. 2015 Apr 12. pii: jbc.M115.646737. PMID:25866208[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Maurer P, T'Sas F, Coutte L, Callens N, Brenner C, Van Lint C, de Launoit Y, Baert JL. FEV acts as a transcriptional repressor through its DNA-binding ETS domain and alanine-rich domain. Oncogene. 2003 May 22;22(21):3319-29. PMID:12761502 doi:http://dx.doi.org/10.1038/sj.onc.1206572
- ↑ Cooper CD, Newman JA, Aitkenhead H, Allerston CK, Gileadi O. Structures of the Ets Domains of Transcription Factors ETV1, ETV4, ETV5 and FEV: Determinants of DNA Binding and Redox Regulation by Disulfide bond formation. J Biol Chem. 2015 Apr 12. pii: jbc.M115.646737. PMID:25866208 doi:http://dx.doi.org/10.1074/jbc.M115.646737
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