dual chaperone role of the c-terminal propeptide in folding and oligomerization of the pore-forming toxin aerolysin双重伴侣蛋白c端前肽在折叠和造孔毒素aerolysin寡聚化.pdfVIP

Dual Chaperone Role of the C-Terminal Propeptide in Folding and Oligomerization of the Pore-Forming Toxin Aerolysin 1. 2. 1¤ 1 3 2 Ioan Iacovache , Matteo T. Degiacomi , Lucile Pernot , Sylvia Ho , Marc Schiltz , Matteo Dal Peraro *, F. Gisou van der Goot1* ´ ´ ´ ´ 1 Global Health Institute, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland, 2 Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne, ´ ´ Lausanne, Switzerland, 3 Laboratoire de Cristallographie, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland 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 us