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Dual chaperone role of the c-terminal propeptide in folding and oligomerization of the pore-forming toxin aerolysin

Iacovache, I.; Degiacomi, M.T.; Pernot, L.; Ho, S.; Schiltz, M.; Dal Peraro, M.; van der Goot, F.G.

Dual chaperone role of the c-terminal propeptide in folding and oligomerization of the pore-forming toxin aerolysin Thumbnail


Authors

I. Iacovache

L. Pernot

S. Ho

M. Schiltz

M. Dal Peraro

F.G. van der Goot



Abstract

Throughout evolution, one of the most ancient forms of aggression between cells or organisms has been the production of proteins or peptides affecting the permeability of the target cell membrane. This class of virulence factors includes the largest family of bacterial toxins, the pore-forming toxins (PFTs). PFTs are bistable structures that can exist in a soluble and a transmembrane state. It is unclear what drives biosynthetic folding towards the soluble state, a requirement that is essential to protect the PFT-producing cell. Here we have investigated the folding of aerolysin, produced by the human pathogen Aeromonas hydrophila, and more specifically the role of the C-terminal propeptide (CTP). By combining the predictive power of computational techniques with experimental validation using both structural and functional approaches, we show that the CTP prevents aggregation during biosynthetic folding. We identified specific residues that mediate binding of the CTP to the toxin. We show that the CTP is crucial for the control of the aerolysin activity, since it protects individual subunits from aggregation within the bacterium and later controls assembly of the quaternary pore-forming complex at the surface of the target host cell. The CTP is the first example of a C-terminal chain-linked chaperone with dual function.

Citation

Iacovache, I., Degiacomi, M., Pernot, L., Ho, S., Schiltz, M., Dal Peraro, M., & van der Goot, F. (2011). Dual chaperone role of the c-terminal propeptide in folding and oligomerization of the pore-forming toxin aerolysin. PLoS Pathogens, 7(7), Article e1002135. https://doi.org/10.1371/journal.ppat.1002135

Journal Article Type Article
Acceptance Date May 11, 2011
Online Publication Date Jul 14, 2011
Publication Date Jul 14, 2011
Deposit Date Jul 26, 2017
Publicly Available Date Mar 29, 2024
Journal PLoS Pathogens
Print ISSN 1553-7366
Electronic ISSN 1553-7374
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 7
Issue 7
Article Number e1002135
DOI https://doi.org/10.1371/journal.ppat.1002135

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

Copyright Statement
© 2011 Iacovache et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.





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