Evidence map›Paper›PMID 24333486›Full record

ArticleJournal of molecular biology2014

Steric mechanism of auto-inhibitory regulation of specific and non-specific DNA binding by the ETS transcriptional repressor ETV6.

Soumya De, Anson C K Chan, H Jerome Coyne, Niraja Bhachech, Ulrike Hermsdorf, Mark Okon, Michael E P Murphy, Barbara J Graves, Lawrence P McIntosh

Open access · hybridAbstract read
In one paragraph

Article in Journal of molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 53 citations in OpenAlex.

  1. Importin-9 recognizes the winged-helix fold of ETS transcription factors to mediate nuclear import.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Stability and dynamics of extradenticle modulates its function.Current research in structural biology · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Comparative structure analysis of the ETSi domain of ERG3 and its complex with the E74 promoter DNA sequence.Acta crystallographica. Section F, Structural biology communications · 2018
    Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Soumya DeDepartment of Biochemistry and Molecular Biology, Department of Chemistry, and Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Anson C K ChanDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
H Jerome CoyneDepartment of Biochemistry and Molecular Biology, Department of Chemistry, and Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Niraja BhachechDepartment of Oncological Sciences, University of Utah School of Medicine, and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112-5550, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA.
Ulrike HermsdorfDepartment of Biochemistry and Molecular Biology, Department of Chemistry, and Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Mark OkonDepartment of Biochemistry and Molecular Biology, Department of Chemistry, and Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Michael E P MurphyDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Barbara J GravesDepartment of Oncological Sciences, University of Utah School of Medicine, and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112-5550, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA.
Lawrence P McIntoshDepartment of Biochemistry and Molecular Biology, Department of Chemistry, and Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z3. Electronic address: mcintosh@chem.ubc.ca.
University of British Columbia · CACanada's Michael Smith Genome Sciences Centre · CAHoward Hughes Medical Institute · USHuntsman Cancer Institute · US

Funding

ZWITTERION SURFACTANT DDMAB FOR IMPROV STABIL OF PROTEINP41RR001209 · NCRR · STANFORD UNIVERSITY · PI GONZALEZ, ANA M · 1985 to 2011
$38.9M
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Transcriptional Control Mechanisms by ETS FactorsR01GM038663 · NIGMS · UNIVERSITY OF UTAH · PI GRAVES, BARBARA J · 1992 to 2015
$3.9M
NCRR NIH HHS P41 RR001209NCRR NIH HHS P41RR001209NIGMS NIH HHS P41 GM103393NIGMS NIH HHS P41GM103393NIGMS NIH HHS R01 GM038663NIGMS NIH HHS R01GM38663
6 · The paper itself

Abstract

DNA binding by the ETS transcriptional repressor ETV6 (or TEL) is auto-inhibited ~50-fold due to an α-helix that sterically blocks its ETS domain binding interface. Using NMR spectroscopy, we demonstrate that this marginally stable helix is unfolded, and not displaced to a non-inhibitory position, when ETV6 is bound to DNA containing a consensus (5')GGAA(3') recognition site. Although significantly lower in affinity, binding to non-specific DNA is auto-inhibited ~5-fold and is also accompanied by helix unfolding. Based on NMR chemical shift perturbations, both specific and non-specific DNA are bound via the same canonical ETS domain interface. However, spectral perturbations are smaller for the non-specific complex, suggesting weaker and less well-defined interactions than in the specific complex. In parallel, the crystal structure of ETV6 bound to a specific DNA duplex was determined. The structure of this complex reveals that a non-conserved histidine residue in the ETS domain recognition helix helps establish the specificity of ETV6 for DNA-binding sites containing (5')GGAA(3')versus(5')GGAT(3'). These studies provide a unified steric mechanism for attenuating ETV6 binding to both specific and non-specific DNA and expand the repertoire of characterized auto-inhibitory strategies utilized to regulate ETS factors.

Indexed as

AnimalsDNAETS Translocation Variant 6 ProteinMagnetic Resonance SpectroscopyMiceProtein BindingProtein Structure, SecondaryProto-Oncogene Proteins c-etsRepressor ProteinsDNAETS Translocation Variant 6 ProteinProto-Oncogene Proteins c-etsRepressor ProteinsETS familyhelix unfoldinginhibitory moduleprotein–DNA interfacewinged helix–turn–helix

Identifiers

PMID24333486
PMCPMC4278593
OpenAlexW2038135364

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.