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

Iacovache, I. and Degiacomi, M.T. and Pernot, L. and Ho, S. and Schiltz, M. and Dal Peraro, M. and van der Goot, F.G. (2011) 'Dual chaperone role of the c-terminal propeptide in folding and oligomerization of the pore-forming toxin aerolysin.', PLoS pathogens., 7 (7). e1002135.

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.

Item Type:Article
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Available under License - Creative Commons Attribution.
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Status:Peer-reviewed
Publisher Web site:https://doi.org/10.1371/journal.ppat.1002135
Publisher 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.
Date accepted:11 May 2011
Date deposited:07 August 2017
Date of first online publication:14 July 2011
Date first made open access:No date available

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