1. Microbiology and Infectious Disease
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Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones

  1. Shehryar Ahmad
  2. Kara L Tsang
  3. Kartik Sachar
  4. Dennis Quentin
  5. Tahmid M Tashin
  6. Nathan P Bullen
  7. Stefan Raunser
  8. Andrew G McArthur
  9. Gerd Prehna  Is a corresponding author
  10. John C Whitney  Is a corresponding author
  1. McMaster University, Canada
  2. University of Manitoba, Canada
  3. Max Planck Institute of Molecular Physiology, Germany
Research Article
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Cite this article as: eLife 2020;9:e62816 doi: 10.7554/eLife.62816

Abstract

Type VI secretion systems (T6SSs) deliver antibacterial effector proteins between neighbouring bacteria. Many effectors harbor N-terminal transmembrane domains (TMDs) implicated in effector translocation across target cell membranes. However, the distribution of these TMD-containing effectors remains unknown. Here we discover prePAAR, a conserved motif found in over 6,000 putative TMD-containing effectors encoded predominantly by 15 genera of Proteobacteria. Based on differing numbers of TMDs, effectors group into two distinct classes that both require a member of the Eag family of T6SS chaperones for export. Co-crystal structures of class I and class II effector TMD-chaperone complexes from Salmonella Typhimurium and Pseudomonas aeruginosa, respectively, reveals that Eag chaperones mimic transmembrane helical packing to stabilize effector TMDs. In addition to participating in the chaperone-TMD interface, we find that prePAAR residues mediate effector-VgrG spike interactions. Taken together, our findings reveal mechanisms of chaperone-mediated stabilization and secretion of two distinct families of T6SS membrane protein effectors.

Article and author information

Author details

  1. Shehryar Ahmad

    Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Kara L Tsang

    Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Kartik Sachar

    Microbiology, University of Manitoba, Winnipeg, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Dennis Quentin

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3825-7066
  5. Tahmid M Tashin

    Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Nathan P Bullen

    Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Stefan Raunser

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9373-3016
  8. Andrew G McArthur

    M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Gerd Prehna

    Microbiology, University of Manitoba, Winnipeg, Canada
    For correspondence
    gerd.prehna@umanitoba.ca
    Competing interests
    The authors declare that no competing interests exist.
  10. John C Whitney

    Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
    For correspondence
    jwhitney@mcmaster.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4423-658X

Funding

Canadian Institutes of Health Research (PJT-156129)

  • John C Whitney

Natural Sciences and Engineering Research Council of Canada (RGPIN-2017-05350)

  • John C Whitney

Natural Sciences and Engineering Research Council of Canada (RGPIN-2018-04968)

  • Gerd Prehna

Canadian Institutes of Health Research (PJT156214)

  • Andrew G McArthur

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

Reviewing Editor

  1. Rajan Sankaranarayanan, CSIR-Centre for Cellular and Molecular Biology, India

Publication history

  1. Received: September 4, 2020
  2. Accepted: December 14, 2020
  3. Accepted Manuscript published: December 15, 2020 (version 1)
  4. Accepted Manuscript updated: December 17, 2020 (version 2)
  5. Version of Record published: December 30, 2020 (version 3)

Copyright

© 2020, Ahmad 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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