title: Spectroscopic characterization of conformational differences between PrPC and PrPSc: an alpha-helix to beta-sheet transition.
abstract: Although no chemical modifications have been found to distinguish the cellular prion protein PrPC from its infectious analogue PrPSc, spectroscopic methods such as Fourier transform infrared (FTIR) spectroscopy reveal a major conformational difference. PrPC is rich in alpha-helix but is devoid of beta-sheet, whereas PrPSc is high in beta-sheet. N-terminal truncation of PrPSc by limited proteolysis does not destroy infectivity but it increases the beta-sheet content and shifts the FTIR absorption to lower frequencies, typical of the cross beta-pleated sheets of amyloids. Thus the formation of PrPSc from PrPC involves a conformational transition in which one or more alpha-helical regions of the protein is converted to beta-sheet. This transition is mimicked by synthetic peptides, allowing predictions of domains of PrP involved in prion diseases.
authors.affiliation: Department of Neurology, University of California, San Francisco 94143-0518.
authors.forename: M A
authors.initials: MA
authors.lastname: Baldwin
authors.forename: K M
authors.initials: KM
authors.lastname: Pan
authors.forename: J
authors.initials: J
authors.lastname: Nguyen
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.forename: D
authors.initials: D
authors.lastname: Groth
authors.forename: A
authors.initials: A
authors.lastname: Serban
authors.forename: M
authors.initials: M
authors.lastname: Gasset
authors.forename: I
authors.initials: I
authors.lastname: Mehlhorn
authors.forename: R J
authors.initials: RJ
authors.lastname: Fletterick
authors.forename: F E
authors.initials: FE
authors.lastname: Cohen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D006224:Cricetinae; D008969:Molecular Sequence Data; D018620:PrPSc Proteins; D011328:Prions / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012608:Scrapie / Q000209:etiology; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D018620:PrPSc Proteins; D011328:Prions