Kinetic Model for 1D aggregation of yeast ``prions''
Abstract
Mammalian prion proteins (PrP) are of public health interest because of mad cow and chronic wasting diseases. Yeast have proteins which can undergo similar reconformation and aggregation processes to PrP; yeast forms are simpler to experimentally study and model. Recent in vitro studies of the SUP35 protein(1), showed long aggregates and pure exponential growth of the misfolded form. To explain this data, we have extended a previous model of aggregation kinetics(2). The model assumes reconformation only upon aggregation, and includes aggregate fissioning and an initial nucleation barrier. We find for sufficiently small nucleation rates or seeding by small dimer concentrations that we can achieve the requisite exponential growth and long aggregates. We will compare to a more realistic stochastic kinetics model and present prelimary attempts to describe recent experiments on SUP35 strains. *-Supported by U.S. Army Congressionally Mandated Research Fund. 1) P. Chien and J.S. Weissman, Nature 410, 223 (2001); http://online.kitp.ucsb.edu/online/bionet03/collins/. 2) J. Masel, V.A.> Jansen, M.A. Nowak, Biophys. Chem. 77, 139 (1999).
- Publication:
-
APS March Meeting Abstracts
- Pub Date:
- March 2004
- Bibcode:
- 2004APS..MAR.A9015K