Prion Diseases pp 209-216 | Cite as

PrPSc typing by N-terminal sequencing and mass spectrometry

  • S. G. Chen
  • W. Zou
  • P. Parchi
  • P. Gambetti
Part of the Archives of Virology. Supplementa book series (ARCHIVES SUPPL, volume 16)


The heterogeneity of the clinicopathological phenotype in human prion diseases is associated with the presence of the different forms of the abnormal prion protein, PrPSc. We have previously shown that PrPSc in FFI and a subtype of familial CJD linked to the D178N mutation can be distinguished by their difference in gel mobility following proteinase K (PK) treatment. To further characterize the structural difference of PrPSc in familial prion diseases, N-terminal sequencing and mass spectrometry were used to identify the protease cleavage sites in PrPSc extracted from affected brains. We found that the main PK cleavage sites of PrPSc are located at residue 97 in FFI, and residue 82 in both CJD178 and a GSS subtype linked to the P102L mutation. The differential accessibility to protease in the native PrPSc suggests that PrPSc exist as distinct conformers in different disease states.


Prion Protein Prion Disease Bovine Spongiform Encephalopathy Fatal Familial Insomnia Human Prion Disease 


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Copyright information

© Springer-Verlag Wien 2000

Authors and Affiliations

  • S. G. Chen
    • 1
  • W. Zou
    • 1
  • P. Parchi
    • 1
  • P. Gambetti
    • 1
  1. 1.Division of Neuropathology, Institute of PathologyCase Western Reserve UniversityClevelandUSA

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