Mammalian Prions Generated from Bacterially Expressed Prion Protein in the Absence of Any Mammalian Cofactors

Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases that are associated with the conformational conversion of a normal prion protein, PrPC, to a misfolded aggregated form, PrPSc. The protein-only hypothesis asserts that PrPSc itself represents the infectious TS...

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Bibliographic Details
Published in:The Journal of biological chemistry 2010-05, Vol.285 (19), p.14083-14087
Main Authors: Kim, Jae-Il, Cali, Ignazio, Surewicz, Krystyna, Kong, Qingzhong, Raymond, Gregory J., Atarashi, Ryuichiro, Race, Brent, Qing, Liuting, Gambetti, Pierluigi, Caughey, Byron, Surewicz, Witold K.
Format: Article
Language:English
Subjects:
Amyloid
Animals
Bacteria
Blotting, Western
Brain - metabolism
Cricetinae
Female
Lipids
Mesocricetus
Molecular Bases of Disease
Neurological Diseases
Nucleic Acids
Prion Diseases - metabolism
Prion Diseases - transmission
Prion Diseases - veterinary
Prions
Protein Conformation
Protein Folding
Protein Misfolding
PrPSc Proteins - isolation & purification
PrPSc Proteins - metabolism
Recombinant Proteins - isolation & purification
Recombinant Proteins - metabolism
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Summary:Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases that are associated with the conformational conversion of a normal prion protein, PrPC, to a misfolded aggregated form, PrPSc. The protein-only hypothesis asserts that PrPSc itself represents the infectious TSE agent. Although this model is supported by rapidly growing experimental data, unequivocal proof has been elusive. The protein misfolding cyclic amplification reactions have been recently shown to propagate prions using brain-derived or recombinant prion protein, but only in the presence of additional cofactors such as nucleic acids and lipids. Here, using a protein misfolding cyclic amplification variation, we show that prions causing transmissible spongiform encephalopathy in wild-type hamsters can be generated solely from highly purified, bacterially expressed recombinant hamster prion protein without any mammalian or synthetic cofactors (other than buffer salts and detergent). These findings provide strong support for the protein-only hypothesis of TSE diseases, as well as argue that cofactors such as nucleic acids, other polyanions, or lipids are non-obligatory for prion protein conversion to the infectious form.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C110.113464