title: Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity.
abstract: The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrPC) whereby it is converted into the pathologic isoform PrPSc. In fatal familial insomnia (FFI), the protease-resistant fragment of PrPSc 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 PrPSc fragment, whereas extracts from the brains of familial and sporadic Creutzfeldt-Jakob disease patients produced the 21-kilodalton PrPSc fragment in these mice. The results presented indicate that the conformation of PrPSc functions as a template in directing the formation of nascent PrPSc and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformation of PrPSc.
authors.affiliation: Department of Neurology, University of California, San Francisco, CA 94143, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Telling
authors.forename: P
authors.initials: P
authors.lastname: Parchi
authors.forename: S J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: P
authors.initials: P
authors.lastname: Cortelli
authors.forename: P
authors.initials: P
authors.lastname: Montagna
authors.forename: R
authors.initials: R
authors.lastname: Gabizon
authors.forename: J
authors.initials: J
authors.lastname: Mastrianni
authors.forename: E
authors.initials: E
authors.lastname: Lugaresi
authors.forename: P
authors.initials: P
authors.lastname: Gambetti
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018620:PrPSc Proteins / Q000032:analysis / Q000737:chemistry*; D017096:Prion Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000635:transmission; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D018620:PrPSc Proteins; D011328:Prions