title: Cryo-EM structure of aerolysin variants reveals a novel protein fold and the pore-formation process.
abstract: Owing to their pathogenical role and unique ability to exist both as soluble proteins and transmembrane complexes, pore-forming toxins (PFTs) have been a focus of microbiologists and structural biologists for decades. PFTs are generally secreted as water-soluble monomers and subsequently bind the membrane of target cells. Then, they assemble into circular oligomers, which undergo conformational changes that allow membrane insertion leading to pore formation and potentially cell death. Aerolysin, produced by the human pathogen Aeromonas hydrophila, is the founding member of a major PFT family found throughout all kingdoms of life. We report cryo-electron microscopy structures of three conformational intermediates and of the final aerolysin pore, jointly providing insight into the conformational changes that allow pore formation. Moreover, the structures reveal a protein fold consisting of two concentric β-barrels, tightly kept together by hydrophobic interactions. This fold suggests a basis for the prion-like ultrastability of aerolysin pore and its stoichiometry.
authors.affiliation: Laboratory of Experimental Morphology, Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3000 Bern 9, Switzerland.
authors.forename: Ioan
authors.initials: I
authors.lastname: Iacovache
authors.affiliation: FEI Company, Achtseweg Noord 5, 5651 GG Eindhoven, The Netherlands.
authors.forename: Sacha
authors.initials: S
authors.lastname: De Carlo
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.|Department of Pharmaceutical Biotechnology, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil.
authors.forename: Nuria
authors.initials: N
authors.lastname: Cirauqui
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.|Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Dal Peraro
authors.affiliation: Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: F Gisou
authors.initials: FG
authors.lastname: van der Goot
authors.affiliation: Laboratory of Experimental Morphology, Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3000 Bern 9, Switzerland.
authors.forename: Benoît
authors.initials: B
authors.lastname: Zuber
mesh_terms: D016980:Aeromonas hydrophila; D001427:Bacterial Toxins; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D007091:Image Processing, Computer-Assisted; D008958:Models, Molecular; D052899:Pore Forming Cytotoxic Proteins / Q000648:ultrastructure*; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D001427:Bacterial Toxins; D052899:Pore Forming Cytotoxic Proteins; C032676:aerolysin