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- Title
Proteolytic processing induces a conformational switch required for antibacterial toxin delivery.
- Authors
Bartelli, Nicholas L.; Passanisi, Victor J.; Michalska, Karolina; Song, Kiho; Nhan, Dinh Q.; Zhou, Hongjun; Cuthbert, Bonnie J.; Stols, Lucy M.; Eschenfeldt, William H.; Wilson, Nicholas G.; Basra, Jesse S.; Cortes, Ricardo; Noorsher, Zainab; Gabraiel, Youssef; Poonen-Honig, Isaac; Seacord, Elizabeth C.; Goulding, Celia W.; Low, David A.; Joachimiak, Andrzej; Dahlquist, Frederick W.
- Abstract
Many Gram-negative bacteria use CdiA effector proteins to inhibit the growth of neighboring competitors. CdiA transfers its toxic CdiA-CT region into the periplasm of target cells, where it is released through proteolytic cleavage. The N-terminal cytoplasm-entry domain of the CdiA-CT then mediates translocation across the inner membrane to deliver the C-terminal toxin domain into the cytosol. Here, we show that proteolysis not only liberates the CdiA-CT for delivery, but is also required to activate the entry domain for membrane translocation. Translocation function depends on precise cleavage after a conserved VENN peptide sequence, and the processed ∆VENN entry domain exhibits distinct biophysical and thermodynamic properties. By contrast, imprecisely processed CdiA-CT fragments do not undergo this transition and fail to translocate to the cytoplasm. These findings suggest that CdiA-CT processing induces a critical structural switch that converts the entry domain into a membrane-translocation competent conformation. Contact-dependent growth inhibition (CDI) is an important mechanism of bacterial competition. Here, Bartelli et al. show that proteolytic processing of a CDI toxin induces a conformational switch required for translocation into target bacteria.
- Subjects
AMINO acid sequence; POISONS; GRAM-negative bacteria; PROTEOLYSIS; PERIPLASM; CYTOPLASM; TOXINS; CYTOSOL
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-32795-y