Bacteria often produce toxins which kill competing bacteria. Colicins, produced by and toxic toEscherichia colibacteria 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.