NR AUJM
AU Tattum,M.H.; Cohen-Krausz,S.; Khalili-Shirazi,A.; Jackson,G.S.; Orlova,E.V.; Collinge,J.; Clarke,A.R.; Saibil,H.R.
TI Elongated oligomers assemble into mammalian PrP amyloid fibrils
QU Journal of Molecular Biology 2006 Mar 31; 357(3): 975-85
PT journal article
AB In prion diseases, the mammalian prion protein PrP is converted from a monomeric, mainly alpha-helical state into beta-rich amyloid fibrils. To examine the structure of the misfolded state, amyloid fibrils were grown from a beta form of recombinant mouse PrP (residues 91-231). The beta-PrP precursors assembled slowly into amyloid fibrils with an overall helical twist. The fibrils exhibit immunological reactivity similar to that of ex vivo PrPsc. Using electron microscopy and image processing, we obtained three-dimensional density maps of two forms of PrP fibrils with slightly different twists. They reveal two intertwined protofilaments with a subunit repeat of approximately 60 A. The repeating unit along each protofilament can be accounted for by elongated oligomers of PrP, suggesting a hierarchical assembly mechanism for the fibrils. The structure reveals flexible crossbridges between the two protofilaments, and subunit contacts along the protofilaments that are likely to reflect specific features of the PrP sequence, in addition to the generic, cross-beta amyloid fold.
MH Amyloid/*chemistry/*metabolism/ultrastructure; Animals; Cysteine/metabolism; Mice; Models, Molecular; Oxidation-Reduction; Prions/*chemistry/*metabolism/ultrastructure; Protein Conformation; Protein Folding; Protein Processing, Post-Translational; Protein Structure, Secondary; Protein Subunits/chemistry/metabolism; Repetitive Sequences, Amino Acid; Research Support, Non-U.S. Gov't
AD MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
SP englisch
PO England