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Cryo‐EM structure of the octameric pore of Clostridium perfringens β‐toxin

Bruggisser, Julia; Iacovache, Ioan; Musson, Samuel C; Degiacomi, Matteo T; Posthaus, Horst; Zuber, Benoît

Cryo‐EM structure of the octameric pore of Clostridium perfringens β‐toxin Thumbnail


Authors

Julia Bruggisser

Ioan Iacovache

Sam Musson samuel.musson@durham.ac.uk
PGR Student Doctor of Philosophy

Matteo T Degiacomi

Horst Posthaus

Benoît Zuber



Abstract

Clostridium perfringens is one of the most widely distributed and successful pathogens producing an impressive arsenal of toxins. One of the most potent toxins produced is the C. perfringens β-toxin (CPB). This toxin is the main virulence factor of type C strains. We describe the cryo-electron microscopy (EM) structure of CPB oligomer. We show that CPB forms homo-octameric pores like the hetero-oligomeric pores of the bi-component leukocidins, with important differences in the receptor binding region and the N-terminal latch domain. Intriguingly, the octameric CPB pore complex contains a second 16-stranded β-barrel protrusion atop of the cap domain that is formed by the N-termini of the eight protomers. We propose that CPB, together with the newly identified Epx toxins, is a member a new subclass of the hemolysin-like family. In addition, we show that the β-barrel protrusion domain can be modified without affecting the pore-forming ability, thus making the pore particularly attractive for macromolecule sensing and nanotechnology. The cryo-EM structure of the octameric pore of CPB will facilitate future developments in both nanotechnology and basic research.

Citation

Bruggisser, J., Iacovache, I., Musson, S. C., Degiacomi, M. T., Posthaus, H., & Zuber, B. (2022). Cryo‐EM structure of the octameric pore of Clostridium perfringens β‐toxin. EMBO Reports, 23(12), Article e54856. https://doi.org/10.15252/embr.202254856

Journal Article Type Article
Acceptance Date Sep 14, 2022
Online Publication Date Dec 6, 2022
Publication Date Dec 6, 2022
Deposit Date Apr 5, 2023
Publicly Available Date Mar 28, 2024
Journal EMBO reports
Print ISSN 1469-221X
Electronic ISSN 1469-3178
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 23
Issue 12
Article Number e54856
DOI https://doi.org/10.15252/embr.202254856

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Open Access. This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.





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