PT  - JOURNAL ARTICLE
AU  - Prins, Rianne C.
AU  - Billerbeck, Sonja
TI  - The signal sequence of yeast killer toxin K2 confers producer self-protection and allows conversion into a modular toxin-antitoxin system
AID  - 10.1101/2023.10.24.563802
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.10.24.563802
4099  - http://biorxiv.org/content/early/2023/10/24/2023.10.24.563802.short
4100  - http://biorxiv.org/content/early/2023/10/24/2023.10.24.563802.full
AB  - Some antimicrobial proteins secreted by yeast, known as yeast killer toxins, also target the producer species itself, necessitating a means of self-protection. Intriguingly, the M2 dsRNA killer virus in Saccharomyces cerevisiae contains a single open reading frame (ORF) that encodes both the pore-forming killer toxin K2 as well as a cognate immunity factor. Here, a systematic deletion screen reveals that expression of a 49-amino acid N-terminal peptide from this ORF is both necessary and sufficient for immunity and that the K2 toxin and this 49-residue immunity peptide can be functionally split into a modular toxin-antitoxin system. Further, the immunity peptide exhibits characteristics of a signal peptide and we thus propose that the K2 signal peptide serves a dual function: 1) Toxin targeting into the secretory pathway, and 2) establishing self-protective immunity. This case further implies that (signal) peptides form a potential source for antimicrobial resistance.Competing Interest StatementThe authors have declared no competing interest.