Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity

Glenn C. Telling, Piero Parchi, Stephen J. DeArmond, Pietro Cortelli, Pasquale Montagna, Ruth Gabizon, James Mastrianni, Elio Lugaresi, Pierluigi Gambetti, Stanley B. Prusiner

Research output: Contribution to journalArticlepeer-review

Abstract

The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrP(C)) whereby it is converted into the pathologic isoform PrP(Sc). In fatal familial insomnia (FFI), the protease- resistant fragment of PrP(Sc) after deglycosylation has a size of 19 kilodaltons, whereas that from other inherited and sporadic prion diseases is 21 kilodaltons. Extracts from the brains of FFI patients transmitted disease to transgenic mice expressing a chimeric human-mouse PrP gene about 200 days after inoculation and induced formation of the 19-kilodalton PrP(Sc) fragment, whereas extracts from the brains of familial and sporadic Creutzfeldt-Jakob disease patients produced the 21-kilodalton PrP(Sc) fragment in these mice. The results presented indicate that the conformation of PrP(Sc) functions as a template in directing the formation of nascent PrP(Sc) and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformation of PrP(Sc).

Original languageEnglish
Pages (from-to)2079-2082
Number of pages4
JournalScience
Volume274
Issue number5295
DOIs
Publication statusPublished - Dec 20 1996

ASJC Scopus subject areas

  • General

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