Structural insight into toxin secretion by contact dependent growth inhibition transporters
- National Institutes of Health, United States
- Georgia Institute of Technology, United States
Abstract
Bacterial contact-dependent growth inhibition (CDI) systems use a type Vb secretion mechanism to export large CdiA toxins across the outer membrane by dedicated outer membrane transporters called CdiB. Here we report the first crystal structures of two CdiB transporters from Acinetobacter baumannii and Escherichia coli. CdiB transporters adopt a TpsB fold, containing a 16-stranded transmembrane β-barrel connected to two periplasmic domains. The lumen of the CdiB pore is occluded by an N-terminal α-helix and the conserved extracellular loop 6; these two elements adopt different conformations in the structures. We identified a conserved DxxG motif located on strand β1 that connects loop 6 through different networks of interactions. Structural modifications of DxxG induce rearrangement of extracellular loops and alter interactions with the N-terminal α-helix, preparing the system for α-helix ejection. Using structural biology, functional assays, and molecular dynamics simulations, we show how the barrel pore is primed for CdiA toxin secretion.
Data availability
Diffraction data have been deposited in PDB under the accession code 6WIL and 6WIM.All data generated or analysed during this study are included in the manuscript and supporting files and videos.
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Author details
Funding
National Institutes of Health (Intramural Research Program)
- Jeremy Guerin
- Istvan Botos
- Susan K Buchanan
National Science Foundation (MCB-1452464)
- Zijian Zhang
- Karl Lundquist
- James C Gumbart
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Structural insight into toxin secretion by contact dependent growth inhibition transporters
eLife 9:e58100.
https://doi.org/10.7554/eLife.58100
