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Cited by 15Bacterial Genetics and BiotechnologyEscherichia coli research studiesBiochemical and Structural Characterization

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Structure of a Rhs effector clade domain provides mechanistic insights into type VI secretion system toxin delivery

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Hayes, Brooke K., Harper, Marina, Venugopal, Hariprasad, Lewis, Jessica M., Wright, Amy, Lee, Han-Chung, Steele, Joel R., Steer, David L., Schittenhelm, Ralf B., Boyce, John D., McGowan, Sheena·2024·Nature Communications
DOI 10.1038/s41467-024-52950-xPMC PMC11461821

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Abstract

The type VI secretion system (T6SS) is a molecular machine utilised by many Gram-negative bacteria to deliver antibacterial toxins into adjacent cells. Here we present the structure of Tse15, a T6SS Rhs effector from the nosocomial pathogen Acinetobacter baumannii . Tse15 forms a triple layered β-cocoon Rhs domain with an N-terminal α-helical clade domain and an unfolded C-terminal toxin domain inside the Rhs cage. Tse15 is cleaved into three domains, through independent auto-cleavage events involving aspartyl protease activity for toxin self-cleavage and a nucleophilic glutamic acid for N-terminal clade cleavage. Proteomic analyses identified that significantly more peptides from the N-terminal clade and toxin domains were secreted than from the Rhs cage, suggesting toxin delivery often occurs without the cage. We propose the clade domain acts as an internal chaperone to mediate toxin tethering to the T6SS machinery. Conservation of the clade domain in other Gram-negative bacteria suggests this may be a common mechanism for delivery.

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Metadata

Authors
Hayes, B. K., Harper, M., Venugopal, H., Lewis, J. M., Wright, A., Lee, H.-C., Steele, J. R., Steer, D. L., Schittenhelm, R. B., Boyce, J. D., & McGowan, S.
Affiliations
Monash University (AU)
Corresponding author
  • Boyce, John D.
  • McGowan, Sheena
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-10-08
Volume
15
Issue
1
Pages
8709-8709
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-52950-x
PMC
PMC11461821
OpenAlex
W4403204445
Cited by
15
References
4
Citations by year
2026: 9 · 2025: 4 · 2024: 2
FWCI
3.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Department of Health | National Health and Medical Research Council (1128981, 1165036)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
Keywords
type VI secretion system, Acinetobacter baumannii, toxin delivery, toxin secretion, Gram-negative bacteria, protein structure
MeSH terms
Type VI Secretion Systems, Protein Domains, Amino Acid Sequence, Bacterial Proteins, Bacterial Toxins, Models, Molecular, Crystallography, X-Ray, Proteomics, Acinetobacter baumannii

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