title: Electron crystallography of the scrapie prion protein complexed with heavy metals.
abstract: The insolubility of the disease-causing isoform of the prion protein (PrP(Sc)) has prevented studies of its three-dimensional structure at atomic resolution. Electron crystallography of two-dimensional crystals of N-terminally truncated PrP(Sc) (PrP 27-30) and a miniprion (PrP(Sc)106) provided the first insights at intermediate resolution on the molecular architecture of the prion. Here, we report on the structure of PrP 27-30 and PrP(Sc)106 negatively stained with heavy metals. The interactions of the heavy metals with the crystal lattice were governed by tertiary and quaternary structural elements of the protein as well as the charge and size of the heavy metal salts. Staining with molybdate anions revealed three prominent densities near the center of the trimer that forms the unit cell, coinciding with the location of the beta-helix that was proposed for the structure of PrP(Sc). Differential staining also confirmed the location of the internal deletion of PrP(Sc)106 at or near these densities.
authors.affiliation: Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, CA 94143, USA.
authors.forename: Holger
authors.initials: H
authors.lastname: Wille
authors.forename: Cédric
authors.initials: C
authors.lastname: Govaerts
authors.forename: Alexander
authors.initials: A
authors.lastname: Borovinskiy
authors.forename: Diane
authors.initials: D
authors.lastname: Latawiec
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Downing
authors.forename: Fred E
authors.initials: FE
authors.lastname: Cohen
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D003198:Computer Simulation; D003461:Crystallography / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D019216:Metals, Heavy / Q000737:chemistry*; D008854:Microscopy, Electron / Q000379:methods*; D008958:Models, Molecular; D018620:PrPSc Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D011487:Protein Conformation
chemical_list: D019216:Metals, Heavy; D018620:PrPSc Proteins