Membrane insertion of α-xenorhabdolysin in near-atomic detail

  1. Evelyn Schubert
  2. Ingrid R Vetter
  3. Daniel Prumbaum
  4. Pawel A Penczek
  5. Stefan Raunser  Is a corresponding author
  1. Max Planck Institute of Molecular Physiology, Germany
  2. The University of Texas, United States

Abstract

α-Xenorhabdolysins (Xax) are α-pore-forming toxins (α-PFT) that form 1-1.3 MDa large pore complexes to perforate the host cell membrane. PFTs are used by a variety of bacterial pathogens to attack host cells. Due to the lack of structural information, the molecular mechanism of action of Xax toxins is poorly understood. Here, we report the cryo-EM structure of the XaxAB pore complex from Xenorhabdus nematophila and the crystal structures of the soluble monomers of XaxA and XaxB. The structures reveal that XaxA and XaxB are built similarly and appear as heterodimers in the 12-15 subunits containing pore, classifying XaxAB as bi-component α-PFT. Major conformational changes in XaxB, including the swinging out of an amphipathic helix are responsible for membrane insertion. XaxA acts as an activator and stabilizer for XaxB that forms the actual transmembrane pore. Based on our results, we propose a novel structural model for the mechanism of Xax intoxication.

Data availability

The electron density map after post-processing has been deposited to the EMDB under accession code EMD-0088. The final model of XaxAB was submitted to the PDB under the accession code 6GY6. Coordinates of XaxA and XaxB in the soluble form have been deposited in the Protein Data Bank under accession codes PDB 6GY8 and PDB 6G47.

The following data sets were generated
    1. Raunser S
    2. Schubert E
    (2018) Crystal structure of XaxA from Xenorhabdus nematophila
    Publicly available at the RCSB Protein Data Bank (accession no: 6GY8).
    1. Raunser S
    2. Schubert E
    (2018) XaxAB pore complex from Xenorhabdus nematophila
    Publicly available at the RCSB Protein Data Bank (accession no: EMD-0088, PDB ID 6GY6).
    1. Raunser S
    2. Schubert E
    (2018) Crystal structure of XaxB from Xenorhabdus nematophila
    Publicly available at the RCSB Protein Data Bank (accession no: 6GY7.

Article and author information

Author details

  1. Evelyn Schubert

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Ingrid R Vetter

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Daniel Prumbaum

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Pawel A Penczek

    Department of Biochemistry and Molecular Biology, The University of Texas, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Stefan Raunser

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    For correspondence
    stefan.raunser@mpi-dortmund.mpg.de
    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

Funding

Max-Planck-Gesellschaft (Open-access funding)

  • Stefan Raunser

European Commission

  • Stefan Raunser

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

Reviewing Editor

  1. Olga Boudker, Weill Cornell Medicine, United States

Version history

  1. Received: May 2, 2018
  2. Accepted: July 15, 2018
  3. Accepted Manuscript published: July 16, 2018 (version 1)
  4. Version of Record published: August 10, 2018 (version 2)

Copyright

© 2018, Schubert 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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  1. Evelyn Schubert
  2. Ingrid R Vetter
  3. Daniel Prumbaum
  4. Pawel A Penczek
  5. Stefan Raunser
(2018)
Membrane insertion of α-xenorhabdolysin in near-atomic detail
eLife 7:e38017.
https://doi.org/10.7554/eLife.38017

Share this article

https://doi.org/10.7554/eLife.38017

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