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Updated: Aug 30, 2025
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Detection of Toxin Translocation into the Host Cytosol by Surface Plasmon Resonance
Published on: January 3, 2012
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Proteolytic processing induces a conformational switch required for antibacterial toxin delivery
Nicholas L Bartelli1, Victor J Passanisi1, Karolina Michalska2,3,4
1Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA.
Nature Communications
|August 29, 2022
Summary
Bacterial CdiA effector proteins deliver toxic CdiA-CT into target cells. Precise cleavage activates the CdiA-CT entry domain for translocation, revealing a critical structural switch for bacterial toxin delivery.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Gram-negative bacteria utilize CdiA effector proteins to inhibit competing bacteria.
- CdiA delivers its toxic CdiA-CT domain into the periplasm of target cells via proteolytic cleavage.
Purpose of the Study:
- To investigate the role of CdiA-CT processing in its translocation into the cytoplasm.
- To elucidate the mechanism by which the CdiA-CT entry domain gains membrane translocation competence.
Main Methods:
- Analysis of CdiA-CT processing and translocation using biochemical and biophysical techniques.
- Investigating the impact of precise versus imprecise proteolytic cleavage on CdiA-CT function.
Main Results:
- Proteolytic cleavage is essential not only for CdiA-CT release but also for activating its N-terminal entry domain for membrane translocation.
- Precise cleavage after the conserved VENN peptide sequence is critical for activating the entry domain's translocation capability.
- Imprecisely processed CdiA-CT fragments fail to transition to a translocation-competent state and cannot enter the cytoplasm.
Conclusions:
- CdiA-CT processing induces a conformational change, switching the entry domain into a membrane-translocation competent state.
- Accurate proteolytic processing is a key regulatory step controlling the delivery of CdiA toxins into bacterial cytoplasm.
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