The infectious agent of
prion diseases is identified with PrP(Sc), a beta-rich, amyloidogenic and partially
protease resistant
isoform of the cellular
glycoprotein, PrP(C). To understand the process of
prion formation in vivo, we and others have studied defined misfolding pathways of recombinant PrP in vitro. The low-level infectivity of the in vitro misfolded murine PrP
amyloid has recently been reported. Here we analyze the in vitro kinetics of
amyloid formation from recombinant human
PrP(90-231) in vitro in the context of two common allelic forms of PrP found in human populations that are associated with differences in
prion disease susceptibility and pathological phenotype. We show that human PrP
amyloid forms readily from its PrP(C)-like state in vitro, that the lag time of the reaction can be further shortened by the presence of a "seed" of pre-formed PrP
amyloid, and that
amyloid propagation is more complex than a simple crystallization process. We further show that the kinetics of
amyloid formation do not differ between the Met129 and Val129 allelomorphs of human PrP, and that
amyloid from each functions as an equally effective seed in heterologous, as in homologous
amyloid reactions. The results could illuminate the process of
amyloid formation in vivo as well as help understanding
prion pathogenesis.