Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones
- McMaster University, Canada
- University of Manitoba, Canada
- Max Planck Institute of Molecular Physiology, Germany
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.
Data availability
X-ray diffraction data for the SciW, SciW:Rhs1 complex, and Tse6:EagT6 complex have been deposited in the PDB under the accession codes 6XRB, 6XRR and 6XRF, respectively.
Article and author information
Author details
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
- Rajan Sankaranarayanan, CSIR-Centre for Cellular and Molecular Biology, India
Version history
- Received: September 4, 2020
- Accepted: December 14, 2020
- Accepted Manuscript published: December 15, 2020 (version 1)
- Accepted Manuscript updated: December 17, 2020 (version 2)
- 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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Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones
eLife 9:e62816.
https://doi.org/10.7554/eLife.62816
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