In vitro conversion of mammalian prion protein into amyloid fibrils displays unusual features.

摘要: The “protein only” hypothesis of prion propagation postulates that the abnormal isoform protein, PrPSc, acts as a causative and transmissible agent disease. In attempt to reconstitute infectivity in vitro, we previously developed cell-free conversion protocol for generating amyloid fibrils from recombinant protein encompassing residues 89−231 (rPrP 89−230) [Baskakov et al. (2002) J. Biol. Chem. 277, 21140]. When inoculated into transgenic mice, these induced disease, which can be efficiently transmitted both wild-type mice [Legname (2004) Science 305, 673]. Here show polymerization rPrPs displays number distinctive kinetic features are not typical by other amyloidogenic polypeptides. Specifically, lag phase showed only modest dependence on concentration, reaction displayed dramatic volume-dependent threshold eff...