NR AUBI
AU Kunes,K.C.; Cox,D.L.; Singh,R.R.P.
TI One-dimensional model of yeast prion aggregation
QU Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics 2005 Nov; 72(5 Pt 1): 051915
PT journal article
AB Mammalian prion proteins (PrP) are of significant public health interest. Yeasts have proteins, which can undergo similar reconformation and aggregation processes to PrP, without posing a threat to the organism. These yeast "prions," such as SUP35, are simpler to experimentally study and model. Recent in vitro studies of the SUP35 protein found long aggregates, pure exponential growth of the misfolded form, and a lag time which depended weakly on the monomer concentration. To explain this data, we have extended a previous model of aggregation kinetics along with a stochastic approach. We assume reconformation only upon aggregation and include aggregate fissioning and an initial nucleation barrier. We find that for sufficiently small nucleation rates or seeding by a small number of preformed nuclei, the models achieve the requisite exponential growth, long aggregates, and a lag time which depends weakly on monomer concentration. The spread in aggregate sizes is well described by the Weibull distribution. All these properties point to the preeminent role of fissioning in the growth of misfolded proteins.
MH Computer Simulation; Crystallization/*methods; Dimerization; Kinetics; *Models, Chemical; *Models, Molecular; Multiprotein Complexes/*chemistry; Prions/*chemistry; Protein Binding; Protein Folding; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Saccharomyces cerevisiae/*chemistry; Saccharomyces cerevisiae Proteins/*chemistry
AD Department of Physics, University of California, Davis, California 95616, USA
SP englisch
PO USA