1. Structural Biology and Molecular Biophysics
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Structural basis of transcription inhibition by the DNA mimic protein Ocr of bacteriophage T7

  1. Fuzhou Ye
  2. Ioly Kotta-Loizou
  3. Milija Jovanovic
  4. Xiaojiao Liu
  5. David TF Dryden
  6. Martin Buck
  7. Xiaodong Zhang  Is a corresponding author
  1. Imperial College London, United Kingdom
  2. University of Durham, United Kingdom
Research Article
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Cite this article as: eLife 2020;9:e52125 doi: 10.7554/eLife.52125

Abstract

Bacteriophage T7 infects Escherichia coli and evades the host restriction/modification system. The Ocr protein of T7 was shown to exist as a dimer mimicking DNA and to bind to host restriction enzymes, thus preventing the degradation of the viral genome by the host. Here we report that Ocr can also inhibit host transcription by directly binding to bacterial RNA polymerase (RNAP) and competing with the recruitment of RNAP by sigma factors. Using cryo electron microscopy, we determined the structures of Ocr bound to RNAP. The structures show that an Ocr dimer binds to RNAP in the cleft, where key regions of sigma bind and where DNA resides during transcription synthesis, thus providing a structural basis for the transcription inhibition. Our results reveal the versatility of Ocr in interfering with host systems and suggest possible strategies that could be exploited in adopting DNA mimicry as a basis for forming novel antibiotics.

Article and author information

Author details

  1. Fuzhou Ye

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Ioly Kotta-Loizou

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Milija Jovanovic

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Xiaojiao Liu

    Department of Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. David TF Dryden

    Department of Biosciences, University of Durham, Durham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Martin Buck

    Life Sciences, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Xiaodong Zhang

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    For correspondence
    xiaodong.zhang@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9786-7038

Funding

Biotechnology and Biological Sciences Research Council (BB/N007816/1)

  • Fuzhou Ye

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Seth Darst, The Rockefeller University, United States

Publication history

  1. Received: September 23, 2019
  2. Accepted: February 8, 2020
  3. Accepted Manuscript published: February 10, 2020 (version 1)

Copyright

© 2020, Ye et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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