1. Biochemistry and Chemical Biology
  2. Microbiology and Infectious Disease
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Structural elucidation of a novel mechanism for the bacteriophage-based inhibition of the RNA degradosome

  1. An Van den Bossche  Is a corresponding author
  2. Steven W Hardwick
  3. Pieter-Jan Ceyssens
  4. Hanne Hendrix
  5. Marleen Voet
  6. Tom Dendooven
  7. Katarzyna J Bandyra
  8. Marc De Maeyer
  9. Abram Aertsen
  10. Jean-Paul Noben
  11. Ben F Luisi  Is a corresponding author
  12. Rob Lavigne  Is a corresponding author
  1. KU Leuven, Belgium
  2. University of Cambridge, United Kingdom
  3. Scietific Institute of Public Health, Belgium
  4. UHasselt, Belgium
Research Article
  • Cited 32
  • Views 2,208
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Cite this article as: eLife 2016;5:e16413 doi: 10.7554/eLife.16413

Abstract

In all domains of life, the catalysed degradation of RNA facilitates rapid adaptation to changing environmental conditions, while destruction of foreign RNA is an important mechanism to prevent host infection. We have identified a virus-encoded protein termed gp37/Dip, which directly binds and inhibits the RNA degradation machinery of its bacterial host. Encoded by giant phage ΦKZ, this protein associates with two RNA binding sites of the RNase E component of the Pseudomonas aeruginosa RNA degradosome, occluding them from substrates and resulting in effective inhibition of RNA degradation and processing. The 2.2 Å crystal structure reveals that this novel homo-dimeric protein has no identifiable structural homologues. Our biochemical data indicate that acidic patches on the convex outer surface bind RNase E. Through the activity of Dip, ΦKZ has evolved a unique mechanism to down regulate a key metabolic process of its host to allow accumulation of viral RNA in infected cells.

Data availability

The following data sets were generated
    1. Steven Hardwick
    (2016) crystal structure
    Publicly available at the RCSB Protein Data Bank (accession no: 5FT1).
    1. An Van den Bossche
    2. Jean-Paul Noben
    (2015) Mass spectrometry data set
    Publicly available at the PRIDE Archive (accession no: PXD003285).

Article and author information

Author details

  1. An Van den Bossche

    Laboratory of Gene Technology, KU Leuven, Leuven, Belgium
    For correspondence
    An.vandenbossche@wiv-isp.be
    Competing interests
    The authors declare that no competing interests exist.
  2. Steven W Hardwick

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Pieter-Jan Ceyssens

    Division of Bacterial diseases, Scietific Institute of Public Health, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  4. Hanne Hendrix

    Laboratory of Gene Technology, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  5. Marleen Voet

    Laboratory of Gene Technology, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  6. Tom Dendooven

    Laboratory of Gene Technology, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  7. Katarzyna J Bandyra

    Department of Biochemsitry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Marc De Maeyer

    Biochemistry, Molecular and Structural Biology Scetion, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  9. Abram Aertsen

    Laboratory of Microbiology, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  10. Jean-Paul Noben

    Biomedical Research Institute and Transnational University Limburg, UHasselt, Diepenbeek, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  11. Ben F Luisi

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    bfl20@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  12. Rob Lavigne

    Laboratory of Gene Technology, KU Leuven, Leuven, Belgium
    For correspondence
    rob.lavigne@biw.kuleuven.be
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7377-1314

Funding

Fonds Wetenschappelijk Onderzoek (G.0599.11 & Scolarship AV)

  • An Van den Bossche
  • Pieter-Jan Ceyssens
  • Hanne Hendrix
  • Rob Lavigne

Agentschap voor Innovatie door Wetenschap en Technologie (SBO 100042)

  • An Van den Bossche
  • Pieter-Jan Ceyssens
  • Rob Lavigne

Onderzoeksraad, KU Leuven (CREA/09/017 & IDO/10/012)

  • Abram Aertsen
  • Rob Lavigne

Wellcome Trust (scholarship SH, BL)

  • Steven W Hardwick
  • Ben F Luisi

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

Reviewing Editor

  1. Gisela Storz, National Institute of Child Health and Human Development, United States

Publication history

  1. Received: April 1, 2016
  2. Accepted: July 18, 2016
  3. Accepted Manuscript published: July 22, 2016 (version 1)
  4. Version of Record published: August 10, 2016 (version 2)

Copyright

© 2016, Van den Bossche 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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