The unstructured domain of colicin N kills E scherichia coli

Summary Bacteria often produce toxins which kill competing bacteria. Colicins, produced by and toxic to E scherichia 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.