title: Crystal structure of an invertebrate cytolysin pore reveals unique properties and mechanism of assembly.
abstract: The invertebrate cytolysin lysenin is a member of the aerolysin family of pore-forming toxins that includes many representatives from pathogenic bacteria. Here we report the crystal structure of the lysenin pore and provide insights into its assembly mechanism. The lysenin pore is assembled from nine monomers via dramatic reorganization of almost half of the monomeric subunit structure leading to a β-barrel pore ∼10 nm long and 1.6-2.5 nm wide. The lysenin pore is devoid of additional luminal compartments as commonly found in other toxin pores. Mutagenic analysis and atomic force microscopy imaging, together with these structural insights, suggest a mechanism for pore assembly for lysenin. These insights are relevant to the understanding of pore formation by other aerolysin-like pore-forming toxins, which often represent crucial virulence factors in bacteria.
authors.affiliation: Department for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
authors.forename: Marjetka
authors.initials: M
authors.lastname: Podobnik
authors.affiliation: Oxford Nanopore Technologies Ltd., Edmund Cartwright House, 4 Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Savory
authors.affiliation: Department for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
authors.forename: Nejc
authors.initials: N
authors.lastname: Rojko
authors.affiliation: Department for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
authors.forename: Matic
authors.identifier: 0000-0003-4131-2177
authors.initials: M
authors.lastname: Kisovec
authors.affiliation: Oxford Nanopore Technologies Ltd., Edmund Cartwright House, 4 Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Wood
authors.affiliation: Oxford Nanopore Technologies Ltd., Edmund Cartwright House, 4 Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Hambley
authors.affiliation: Oxford Nanopore Technologies Ltd., Edmund Cartwright House, 4 Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pugh
authors.affiliation: Oxford Nanopore Technologies Ltd., Edmund Cartwright House, 4 Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK.
authors.forename: E Jayne
authors.initials: EJ
authors.lastname: Wallace
authors.affiliation: Oxford Nanopore Technologies Ltd., Edmund Cartwright House, 4 Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: McNeill
authors.affiliation: Oxford Nanopore Technologies Ltd., Edmund Cartwright House, 4 Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Bruce
authors.affiliation: Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
authors.forename: Idlir
authors.initials: I
authors.lastname: Liko
authors.affiliation: Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Allison
authors.affiliation: Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
authors.forename: Shahid
authors.initials: S
authors.lastname: Mehmood
authors.affiliation: Lipid Biology Laboratory, RIKEN Institute, Wako 351-0198, Japan.
authors.forename: Neval
authors.initials: N
authors.lastname: Yilmaz
authors.affiliation: Lipid Biology Laboratory, RIKEN Institute, Wako 351-0198, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Robert J C
authors.initials: RJ
authors.lastname: Gilbert
authors.affiliation: Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
authors.affiliation: Oxford Nanopore Technologies Ltd., Edmund Cartwright House, 4 Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK.
authors.forename: Lakmal
authors.initials: L
authors.lastname: Jayasinghe
authors.affiliation: Department for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
authors.forename: Gregor
authors.identifier: 0000-0002-9916-8465
authors.initials: G
authors.lastname: Anderluh
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000737:chemistry* / Q000378:metabolism*; D007448:Invertebrates / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D016062:Porosity; D017433:Protein Structure, Secondary; D014118:Toxins, Biological / Q000737:chemistry
chemical_list: D003603:Cytotoxins; D014118:Toxins, Biological; C107040:lysenin