4uno: Difference between revisions
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==Crystal structure of the ETS domain of human ETV5 in complex with DNA== | ==Crystal structure of the ETS domain of human ETV5 in complex with DNA== | ||
<StructureSection load='4uno' size='340' side='right' caption='[[4uno]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='4uno' size='340' side='right'caption='[[4uno]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4uno]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UNO OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4uno]] 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=4UNO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UNO FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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]] 1.95Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <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=4uno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uno OCA], [https://pdbe.org/4uno PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uno RCSB], [https://www.ebi.ac.uk/pdbsum/4uno PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uno ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ETV5_HUMAN ETV5_HUMAN] Binds to DNA sequences containing the consensus nucleotide core sequence GGAA. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4uno" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Aitkenhead | [[Category: Homo sapiens]] | ||
[[Category: Arrowsmith | [[Category: Large Structures]] | ||
[[Category: Bountra | [[Category: Synthetic construct]] | ||
[[Category: Burgess-Brown | [[Category: Aitkenhead H]] | ||
[[Category: Cooper | [[Category: Arrowsmith CH]] | ||
[[Category: Bountra C]] | |||
[[Category: Edwards | [[Category: Burgess-Brown N]] | ||
[[Category: Fitzpatrick | [[Category: Cooper CDO]] | ||
[[Category: Gileadi | [[Category: Edwards A]] | ||
[[Category: Kopec | [[Category: Fitzpatrick F]] | ||
[[Category: Newman | [[Category: Gileadi O]] | ||
[[Category: Pinkas | [[Category: Kopec J]] | ||
[[Category: Shrestha | [[Category: Newman JA]] | ||
[[Category: Tallant | [[Category: Pinkas DM]] | ||
[[Category: | [[Category: Shrestha L]] | ||
[[Category: Tallant C]] | |||
[[Category: Von Delft F]] | |||
Latest revision as of 13:31, 10 January 2024
Crystal structure of the ETS domain of human ETV5 in complex with DNACrystal structure of the ETS domain of human ETV5 in complex with DNA
Structural highlights
FunctionETV5_HUMAN Binds to DNA sequences containing the consensus nucleotide core sequence GGAA. Publication Abstract from PubMedEts 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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