Membrane insertion of α-xenorhabdolysin in near-atomic detail

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Cite this article as: eLife 2018;7:e38017 doi: 10.7554/eLife.38017

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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.

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Author details

Evelyn Schubert

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany

Competing interests
The authors declare that no competing interests exist.
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.
Daniel Prumbaum

Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany

Competing interests
The authors declare that no competing interests exist.
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.
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.

"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

Olga Boudker, Weill Cornell Medicine, United States

Publication history

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

Copyright

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.