Epitopes described in "Molecular distinction between pathogenic and infectious properties of the prion protein."

Article Authors:Roberto Chiesa; Pedro Piccardo; Elena Quaglio; Bettina Drisaldi; San Ling Si-Hoe; Masaki Takao; Bernardino Ghetti; David A Harris
Article Title:Molecular distinction between pathogenic and infectious properties of the prion protein.
Reference Detail
Reference ID:1001769
Abstract:Tg(PG14) mice express a prion protein (PrP) with a nine-octapeptide insertion associated with a human familial prion disease. These animals spontaneously develop a fatal neurodegenerative disorder characterized by ataxia, neuronal apoptosis, and accumulation in the brain of an aggregated and weakly protease-resistant form of mutant PrP (designated PG14(spon)). Brain homogenates from Tg(PG14) mice fail to transmit disease after intracerebral inoculation into recipient mice, indicating that PG14(spon), although pathogenic, is distinct from PrP(Sc), the infectious form of PrP. In contrast, inoculation of Tg(PG14) mice with exogenous prions of the RML strain induces accumulation of PG14(RML), a PrP(Sc) form of the mutant protein that is infectious and highly protease resistant. Like PrP(Sc), both PG14(spon) and PG14(RML) display conformationally masked epitopes in the central and octapeptide repeat regions. However, these two forms differ profoundly in their oligomeric states, with PG14(RML) aggregates being much larger and more resistant to dissociation. Our analysis provides new molecular insight into an emerging puzzle in prion biology, the discrepancy between the infectious and neurotoxic properties of PrP.
Affiliations:Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Reference Type:Literature
PubMed ID:12805461
Journal:J Virol
Journal Volume:77
Article Pages:7611-22
Journal ISSN:1098-5514
Article Chemical List:Prions
Article MeSH List:Animals; Mice; Mice, Transgenic; Prions(chemistry; genetics; pathogenicity); Protein Conformation; Scrapie(etiology)
Curation Last Updated:2015-06-05 00:29:27