Species and Strain Glycosylation Patterns of PrPSc

Abstract

BackgroundA key event in transmissible spongiform encephalopathies (TSEs) is the conversion of the soluble, protease-sensitive glycosylated prion protein (PrPC) to an abnormally structured, aggregated and partially protease-resistant isoform (PrPSc). Both PrP isoforms bear two potential glycosylation sites and thus in a typical western blot with an anti-PrP antibody three distinct bands appear, corresponding to the di-, mono- or unglycosylated forms of the protein. The relative intensity and electrophoretic mobility of the three bands are characteristic of each TSE strain and have been used to discriminate between them.Methodology/Principal FindingsIn the present study we used lectin-based western blotting to evaluate possible variations in composition within sugar chains carried by PrPSc purified from subjects affected with different TSEs. Our findings indicate that in addition to the already well-documented differences in electrophoretic mobility and amounts of the glycosylated PrPSc forms, TSE strains also vary in the abundance of specific N-linked sugars of the PrPSc protein.Conclusions/SignificanceThese results imply that PrP glycosylation might fine-tune the conversion of PrPC to PrPSc and could play an accessory role in the appearance of some of the characteristic features of TSE strains. The differences in sugar composition could also be used as an additional tool for discrimination between the various TSEs.