The Mechanism of Toxicity in HET-S/HET-s Prion Incompatibility

摘要: The HET-s protein from the filamentous fungus Podospora anserina is a prion involved in cell death reaction termed heterokaryon incompatibility. This observed at point of contact between two genetically distinct strains when one harbors (in form amyloid aggregates) and other expresses soluble HET-S (96% identical to HET-s). How interaction with brings about remains unknown; however, it was recently shown that this leads relocalization cytoplasm periphery change associated death. Here, we present detailed insights into mechanism which non-toxic converts an integral membrane destabilizes membranes. We liposomal defects approximately 10 up 60 nm size transmission electron microscopy images freeze-fractured proteoliposomes were formed mixtures amyloids. In liposome leakage assays, has innate ability associate disrupt lipid membranes activity greatly enhanced exposed Solid-state nuclear magnetic resonance (NMR) analyses revealed induces prion-forming domain adopt β-solenoid fold (previously HET-s) disrupts globular HeLo domain. These data indicate upon prion, partially unfolds, thereby exposing previously buried ∼34-residue N-terminal transmembrane segment. liberation segment targets where further oligomerizes, leading loss integrity. thus appears display features are reminiscent pore-forming toxins.