Structures of the Ets protein DNA-binding domains of transcription factors Etv1, Etv4, Etv5, and Fev determinants of DNA binding and redox regulation by disulfide bond formation.Report as inadecuate




Structures of the Ets protein DNA-binding domains of transcription factors Etv1, Etv4, Etv5, and Fev determinants of DNA binding and redox regulation by disulfide bond formation. - Download this document for free, or read online. Document in PDF available to download.

Reference: Cooper, CDO, Newman, JA, Aitkenhead, H et al., (2015). Structures of the Ets protein DNA-binding domains of transcription factors Etv1, Etv4, Etv5, and Fev determinants of DNA binding and redox regulation by disulfide bond formation. Journal of Biological Chemistry, 290 (22), 13692-13709.Citable link to this page:

 

Structures of the Ets protein DNA-binding domains of transcription factors Etv1, Etv4, Etv5, and Fev determinants of DNA binding and redox regulation by disulfide bond formation.

Abstract: Ets transcription factors, which share the conserved Ets DNAbinding 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; however, 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 proteinDNA 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 that may control the activity of this subset of oncogenic Ets transcription factors.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:2015-04-07Notes:© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice — Final version free via Creative Commons CC-BY license.

Bibliographic Details

Publisher: American Society for Biochemistry and Molecular Biology

Publisher Website: http://www.asbmb.org/

Journal: Journal of Biological Chemistrysee more from them

Publication Website: http://www.jbc.org/

Volume: 290

Issue: 22

Extent: 13692-13709

Issue Date: 2015-04

pages:13692-13709Identifiers

Urn: uuid:f79de7a2-6206-456b-9624-305871d6b91b

Source identifier: 518379

Eissn: 1083-351X

Doi: https://doi.org/10.1074/jbc.m115.646737

Issn: 0021-9258 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Humans Neoplasms Disulfides Oxygen DNA-Binding Proteins Adenovirus E1A Proteins Proto-Oncogene Proteins Nuclear Proteins Recombinant Proteins Transcription Factors DNA Chromatography, Liquid Spectrometry, Mass, Electrospray Ionization Mutagenesis, Site-Directed Gene Expression Regulation Amino Acid Sequence Protein Conformation Protein Binding Sequence Homology, Amino Acid Oxidation-Reduction Models, Molecular Molecular Sequence Data Proto-Oncogene Proteins c-ets Protein Multimerization Tiny URL: pubs:518379

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Author: Cooper, CDO - Oxford, Colleges and Halls, Linacre College - - - Newman, JA - Oxford, MSD, NDM, Structural Genomics Consortium - -

Source: https://ora.ox.ac.uk/objects/uuid:f79de7a2-6206-456b-9624-305871d6b91b



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