Prion-like characteristics of the bacterial protein Microcin E492

Microcin E492 (Mcc) is a pore-forming bacteriotoxin. Mcc activity is inhibited at the stationary phase by formation of amyloid-like aggregates in the culture. Here we report that, in a similar manner as prions, Mcc naturally exists as two conformers: a β-sheet-rich, protease-resistant, aggregated, inactive form (Mcc(ia)), and a soluble, protease-sensitive, active form (Mcc(a)). The exogenous addition of culture medium containing Mcc(ia) or purified in vitro-generated Mcc(ia) into the culture induces the rapid and efficient conversion of Mcc(a) into Mcc(ia), which is maintained indefinitely after passaging, changing the bacterial phenotype. Mcc(ia) prion-like activity is conformation-dependent and could be reduced by immunodepleting Mcc(ia). Interestingly, an internal region of Mcc shares sequence similarity with the central domain of the prion protein, which is key to the formation of mammalian prions. A synthetic peptide spanning this sequence forms amyloid-like fibrils in vitro and is capable of inducing the conversion of Mcc(a) into Mcc(ia) in vivo, suggesting that this region corresponds to the prion domain of Mcc. Our findings suggest that Mcc is the first prokaryotic protein with prion properties which harnesses prion-like transmission to regulate protein function, suggesting that propagation of biological information using a prion-based conformational switch is an evolutionary conserved mechanism.