The unstructured domain of colicin N kills Escherichia coli

Bacteria often produce toxins which kill competing bacteria. Colicins, produced by and toxic to Escheri-chia coli bacteria are three-domain proteins so effi-cient 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 unstruc-tured. 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. Further-more it causes ion leakage from cells but, unlike known antimicrobial peptides (AMPs) with this prop-erty, 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 dis-ruption, via receptor mediated binding of a soluble peptide, may reveal a new target for the development of highly specific antibacterials