PrP structure



The normal PrP structure, that of PrPC (the cellular form of PrP, prion-related protein), in its mature form, is 253 amino acids long including two signal sequences in the amino- and carboxy- terminal ends which are removed during post-translational modification. Prion protein contains 5 amino-terminal octapeptide repeats, two glycosylated sites at Asn181 and Asn197 for human and Syrian Hamster PrP, Asn180 and Asn196 for murine PrP and one disulfide bond between Cys179 of the second helix and Cys214 of the third helix (human PrPC numbering). The protein attaches to the outer surface of the cell membrane by glycosylphosphatidylinositol anchor at its C-terminal Ser231.

Spectroscopic Analysis
The NMR structure of the full length and N-terminally truncated forms of human PrP prion protein revealed an N-terminal flexible and disordered region PrP23-126 and an orthogonal bundle (OB) structured C-terminal globular domain PrP127-231 (Figure 1). The human PrP globular domain containing three α-helices comprising residues 144-154 (H1), 173-194 (H2), 200-228 (H3) and an anti-parallel β sheet consisting of two short strands comprising residues 128-131 (S1) and 161-164 (S2). All NMR studies could identify the three alpha helices, although with slightly different length but showed differences for the less defined antiparallel beta sheet.