Fig. 4.

The simplest model of recombinant PrP amyloid consistent with present experimental data. (A) The monomeric folded domain (residues 120–231) of human PrP. Residues determined herein to form the core of the amyloid are highlighted in red. (B) Electron micrograph of PrP amyloid fibrils. (Scale bar: 100 nm.) The width of the fibrils (arrows) was determined to be 12 ± 1 nm. (C) Model for the fold of the PrP amyloid core (residues 159–219) consistent with the present data. The native disulfide bond is shown in green, charged residues are colored red (negative) and blue (positive), and potential N-linked glycosylation sites are labeled. The only charged residue positioned in the dry interface, E211, is in hydrogen-bonding distance of Q186. The exact identity of β-strands is unknown, and orientation of the most N-terminal strands is arbitrary. (D) In-register stacking motif of nearly planar PrP monomers in the amyloid modeled with tight interdigitation of the side chains. (E) Rotated structure showing the network of intermolecular hydrogen bonding. The arrow indicates the long axis of the fibril.