Figure 5.

Proposed mechanism for prion conversion involving asparagine/glutamine residues in discrete segments of bank vole PrP^C. A, a ribbon diagram of the NMR BvPrP^C structure (Protein Data Bank code 2K56; Ref. 27) with critical Asn/Gln residues shown in magenta. The N-terminal domain of PrP^C (residues 97–118, gray) is modeled using Rosetta software (63). Residues 23–96 are not shown. B, another view of the NMR BvPrP^C structure rotated horizontally by 90°. C, zipper structure from PrP^Sc peptide (residues 170–175; Protein Data Bank code 3VFA; Ref. 36) fibril demonstrating that alignment of Asn/Gln residues along the length of the fibril axis promotes side chain hydrogen bonds in a motif known as an asparagine/glutamine-ladder. β-Strands are represented by gray arrows, Asm¹⁷⁴ residues are shown in magenta, Gln¹⁷² residues are in cyan, and side chain hydrogen bonds in the asparagine/glutamine-ladder are indicated by black dotted lines.