title: Biochemical and conformational variability of human prion strains in sporadic Creutzfeldt-Jakob disease.
abstract: The pathogenesis of prion (PrP) diseases is thought to be related to conformational changes of a normal cellular protein, PrPC, into a protease resistant protein called PrPSc, which is infectious by itself. A difficulty with this 'protein only' hypothesis is the existence of numerous PrP strains, that require PrPSc to have multiple conformations. Sporadic Creutzfeldt-Jakob disease (CJD), which accounts for nearly 80% of human prionoses, was reported to include at least two 'strains' termed types 1 and 2 which differ by electrophoretic patterns of their proteinase K (PK)-resistant fragments (PrP27-30). We have analyzed the biochemical and structural properties of PrPSc and PrP27-30 isolates from six sporadic CJD patients. Fourier transform-infra-red spectroscopy, PrP27-30 glycosylation patterns and studies of PK sensitivity revealed a striking heterogeneity. Furthermore, one isolate yielded a PrP27-30 fragment with a lower mobility clearly different from previously described sporadic CJD types. Although the average beta-sheet content was higher among type 1 isolates, there was overlap between the two types. Our study suggests that human sporadic CJD-related prions display a significant heterogeneity.
authors.affiliation: Department of Pathology, New York University School of Medicine, NY 10016, USA.
authors.forename: P
authors.initials: P
authors.lastname: Aucouturier
authors.forename: R J
authors.initials: RJ
authors.lastname: Kascsak
authors.forename: B
authors.initials: B
authors.lastname: Frangione
authors.forename: T
authors.initials: T
authors.lastname: Wisniewski
mesh_terms: D000368:Aged; D015153:Blotting, Western; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000737:chemistry*; D018622:PrP 27-30 Protein / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D018620:PrPSc Proteins / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D018620:PrPSc Proteins; D018622:PrP 27-30 Protein