title: The unstructured domain of colicin N kills Escherichia coli.
abstract: Bacteria often produce toxins which kill competing bacteria. Colicins, produced by and toxic to Escherichia coli bacteria are three-domain proteins so efficient that one molecule can kill a cell. The C-terminal domain carries the lethal activity and the central domain is required for surface receptor binding. The N-terminal domain, required for translocation across the outer membrane, is always intrinsically unstructured. It has always been assumed therefore that the C-terminal cytotoxic domain is required for the bactericidal activity. Here we report the unexpected finding that in isolation, the 90-residue unstructured N-terminal domain of colicin N is cytotoxic. Furthermore it causes ion leakage from cells but, unlike known antimicrobial peptides (AMPs) with this property, shows no membrane binding behaviour. Finally, its activity remains strictly dependent upon the same receptor proteins (OmpF and TolA) used by full-length colicin N. This mechanism of rapid membrane disruption, via receptor mediated binding of a soluble peptide, may reveal a new target for the development of highly specific antibacterials.
authors.affiliation: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle- upon-Tyne, NE2 4HH, UK.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Johnson
authors.forename: Helen
authors.initials: H
authors.lastname: Ridley
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Pengelly
authors.forename: Mohd Zulkifli
authors.initials: MZ
authors.lastname: Salleh
authors.forename: Jeremy H
authors.initials: JH
authors.lastname: Lakey
mesh_terms: D002462:Cell Membrane / Q000187:drug effects; D003087:Colicins / Q000633:toxicity*; D004252:DNA Mutational Analysis; D004926:Escherichia coli / Q000187:drug effects* / Q000502:physiology; D029968:Escherichia coli Proteins / Q000378:metabolism; D050296:Microbial Viability / Q000187:drug effects*; D018272:Porins / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D003087:Colicins; D029968:Escherichia coli Proteins; C109237:OmpF protein; D018272:Porins; C062093:tolA protein, E coli