SYNOPSIS Prion Folding Sends a Death Signal in Fungus

Prions are kind of like Batman—they have a bad reputation, but they can also serve a number of good purposes. While prion domains—folded regions of proteins that can induce similar folding in other susceptible proteins—are responsible for the human prion diseases and may be involved in other neurodegenerative diseases as well, they have also been linked to normal pro-cesses of memory and innate immunity. In the fungus Podospora anserina, the protein HET-S includes a prion-forming domain, which, when it folds into the so-called beta-solenoid conformation, causes the protein to embed in the plasma membrane, where it forms a pore that ultimately results in cell death. One trigger for this folding is interaction with a very similar protein (called HET-s) from a different strain of the same fungus. When the two strains meet, their prion-mediated interaction pre-vents them from fusing and limits the transmission of pathogens between strains. But HET-s isn’t the only protein that induces prion folding in HET-S, according to a new study by Asen Daskalov, Sven Saupe, and colleagues in this issue of PLOS Biology. They show that the HET-S conformation change can be triggered through interaction with a member of a widely distributed protein family, suggesting that prion-based signal transduction may be more common than currently appreciated (Fig. 1). Figure 1. The fungal NOD-like receptor NWD2 controls activation of the HET-S pore-forming protein. The signaling process is based on the formation and transmission of an amyloid prion structure. doi:10.1371/journal.pbio.1002058.g00