The signal peptide of yeast killer toxin K2 confers producer self-protection and allows conversion into a modular toxin-immunity system

Some microbial toxins also target the producer species itself, necessitating a means of self-protection. The M2 double-stranded RNA (dsRNA) killer virus in Saccharomyces cerevisiae contains a single open reading frame (ORF) encoding both the secreted pore-forming toxin K2 as well as a cognate immunity factor. Here, we show that expression of a 49-amino acid N-terminal peptide from the K2 precursor is both necessary and sufficient for immunity. This immunity peptide simultaneously functions as a signal peptide for toxin secretion and protects the cell against the cytotoxic K2 α subunit. The K2 toxin and immunity factor can be functionally separated into two ORFs, yielding a modular toxin-immunity system. This case further shows how a (signal) peptide can carry the potential for providing cellular protection against an antimicrobial toxin.