Fitting Yeast and Mammalian Prion Aggregation Kinetic Data with the Finke−Watzky Two-Step Model of Nucleation and Autocatalytic Growth†

Recently, we reported 14 amyloid protein aggregation kinetic data sets that were fit using the “Ockham’s razor”/minimalistic Finke−Watzky (F−W) two-step model of slow nucleation (A → B, rate constant k1) and fast autocatalytic growth (A + B → 2B, rate constant k2), yielding quantitative (average) rate constants for nucleation (k1) and growth (k2), where A is the monomeric protein and B is the polymeric protein [Morris, A. M., et al. (2008) Biochemistry 47, 2413−2427]. Herein, we apply the F−W model to 27 representative prion aggregation kinetic data sets obtained from the literature. Each prion data set was successfully fit with the F−W model, including three different yeast prion proteins (Sup35p, Ure2p, and Rnq1p) as well as mouse and human prions. These fits yield the first quantitative rate constants for the steps of nucleation and growth in prion aggregation. Examination of a Sup35p system shows that the same rate constants are obtained for nucleation and for growth within experimental error, regardl...