title: The kinetics of proteinase K digestion of linear prion polymers.
abstract: Transmissible spongiform encephalopathies such as scrapie are caused by a protein-only infectious agent, known as a prion. It is not clear how a protein can be capable of replicating itself, and the mechanism remains controversial. One influential model hypothesizes that prions are nucleated, macroscopically linear polymers. We investigated the theoretical kinetics of this model and derived predictions which could be used to test the model. In the model, the polymerization and depolymerization rates are independent polymer size. This leads to an exponential size distribution at equilibrium. In agreement with a prediction stemming from this size distribution, the average size of PrP-res polymers was proportional to the square root of the concentration of PrP-res in a published study of in vitro conversion. Prion digestion by proteinase K (PK) is predicted to be biphasic. The second phase of digestion should be virtually independent of the PK concentration and should depend on the initial size distribution of prion polymers. For initially equilibrated polymers with an exponential size distribution, phase two digestion is exponential at a predicted rate. This rate varies in a defined way with the concentration used for equilibration and with other parameters which affect the average polymer size.
authors.affiliation: Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, University of Oxford, UK. joanna@volterra.zoo.ox.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Masel
authors.forename: V A
authors.initials: VA
authors.lastname: Jansen
mesh_terms: D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D019286:Endopeptidase K / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary
chemical_list: D001704:Biopolymers; D011328:Prions; D019286:Endopeptidase K