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Research article2006Peer reviewedOpen access

Characterization of proteinase K-resistant N- and C-terminally truncated PrP in Nor98 atypical scrapie

Klingeborn M, Wik L, Simonsson M, Renstrom LHM, Ottinger T, Linne T

Abstract

An increasing number of scrapie cases with atypical characteristics, designated Nor98, have recently been recognized. Here, the proteinase K (PK)-resistant prion protein (PrP) fragments from two Swedish cases of Nor98 atypical scrapie have been characterized. The prominent, fast-migrating band in the distinct Nor98 Western immunoblot electrophoretic profile was determined to be of 7 kDa in size and was accordingly designated Nor98-PrP7. The antigenic composition of Nor98-PrP7, as assayed by a panel of anti-PrP antibodies, revealed that this fragment comprised a mid-region of PrP from around as 85 to 148. N- and C-terminally truncated fragments spanning the mid-region of PrP have only been observed in the genetic prion disorder Gerstmann-Strdussler-Scheinker disease. It is shown here that the long-term PK resistance of Nor98-PrP7 is reduced compared with that of PrPres in classical scrapie. Enzymic deglycosylation did not change the distinct electrophoretic profile of Nor98-PrP7. A previously unidentified, PK-resistant, C-terminal PrP fragment of around 24 kDa was detected and its PK resistance was investigated. After deglycosylation, this fragment migrated as a 14 kDa polypeptide and was designated PrP-CTF14. Antigenic determination and the size of 14 kDa suggested a fragment spanning approximately as 120-233. The existence of two PK-resistant PrP fragments, Nor98-PrP7 and PrP-CTF14, that share an overlapping region suggests that at least two distinct PrP conformers with different PK-resistant cores are present in brain extracts from Nor98-affected sheep. The structural gene of PrP in three Nor98-affected sheep was analysed, but no mutations were found that could be correlated to the aberrant PK-resistant profile observed

Published in

Journal of General Virology
2006, Volume: 87, pages: 1751-1760 Publisher: SOC GENERAL MICROBIOLOGY

      SLU Authors

    • Klingeborn, Mikael

      • Department of Molecular Biosciences, Swedish University of Agricultural Sciences
      • Linne, Tommy

        • Department of Molecular Biosciences, Swedish University of Agricultural Sciences
        • Simonsson, Magnus

          • Department of Molecular Biosciences, Swedish University of Agricultural Sciences
          • Wik, Lotta

            • Department of Molecular Biosciences, Swedish University of Agricultural Sciences
            • Ottinger, Therese

              • Department of Molecular Biosciences, Swedish University of Agricultural Sciences

            UKÄ Subject classification

            Veterinary Science
            Animal and Dairy Science

            Publication identifier

            DOI: https://doi.org/10.1099/vir.0.81618-0

            Permanent link to this page (URI)

            https://res.slu.se/id/publ/8626