Conformational polymorphism of the amyloidogenic and neurotoxic peptide homologous to residues 106-126 of the prion protein.

摘要: Prion-related encephalopathies are characterized by cerebral accumulation of a post-translationally modified form the cellular prion protein (PrPC), designated PrPSc. Evidence suggests that conversion from PrPC to PrPSc involves changes in secondary structure leading an increase beta-sheet content. We have previously shown synthetic peptide homologous residues 106-126 human PrP, belonging predicted alpha-helical domain, exhibits conformation, forms amyloid-like fibrils, and is neurotoxic vitro. The present study investigated how different chemicophysical conditions such as pH ionic strength or membrane-like environment influenced this peptide. PrP exhibited predominantly 200 mM phosphate buffer, 5.0, but combination random coil 7.0, deionized water. addition trifluoroethanol (50% final concentration) solutions water induced appearance structure, did not modify conformation dissolved 5.0. In presence micelles formed 5% solution sodium dodecyl sulfate, showed high content alpha-helix. When was 5 7.4, incubated with liposomes, it changed prevalently conformation. environment-dependent conformational polymorphism its marked tendency stable structures at acidic could account for shift alpha-helix associated PrPSc, which occurs most likely endosomal-lysosomal compartment.