Mammalian prions generated from bacterially expressed prion protein in the absence of any mammalian cofactors

J Biol Chem. 2010 May 7;285(19):14083-7. doi: 10.1074/jbc.C110.113464. Epub 2010 Mar 19.


Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases that are associated with the conformational conversion of a normal prion protein, PrP(C), to a misfolded aggregated form, PrP(Sc). The protein-only hypothesis asserts that PrP(Sc) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Blotting, Western
  • Brain / metabolism
  • Cricetinae
  • Female
  • Lipids*
  • Mesocricetus
  • Nucleic Acids*
  • PrPSc Proteins / isolation & purification
  • PrPSc Proteins / metabolism*
  • Prion Diseases / metabolism*
  • Prion Diseases / transmission
  • Prion Diseases / veterinary
  • Protein Folding
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism*


  • Lipids
  • Nucleic Acids
  • PrPSc Proteins
  • Recombinant Proteins