Figure 1 Organization and structural properties of the mouse prion protein. (A) Scheme of the organization of the mouse prion protein (numeration according to the human prion protein). In the mature form of the protein the N-terminal signal peptide (N-terminal green box) is cleaved off and the C-terminal peptide (C-terminal green box) is replaced by a GPI anchor at Ser-231. The N-terminal unstructured part of the protein contains five octarepeats (magenta boxes), two positively charged amino acid clusters CC1 and CC2 (orange boxes) and a highly conserved hydrophobic polypeptide segment comprising residues 111–134 (yellow box). The folded C-terminal domain contains three α-helices H1–H3 (blue boxes) and a short antiparallel β-sheet (indicated by two black arrows). Helices α2 and α3 are connected by a single disulfide bridge between Cys-179 and Cys-214. The protein also contains two potential glycosylation sites at amino acid positions 181 and 197 (light blue ellipses). (B) Three-dimensional structure of mPrP(121–231). The three α-helices are shown in blue and the antiparallel β-sheet in green. (C) Electron micrographs of negatively stained recombinant mouse fibrils. The bar represents 100 nm.
Figure 2 Location of point mutations in the three-dimensional structure of hPrP(121–230) that are associated with familial prion diseases. The backbone is shown in grey and the side chains of the residues associated with the mutations for inherited fCJD are shown in red (A), for GSS in blue (B) and fFFI in magenta (C). The polymorphism at position 129 is indicated in green. The molecules were generated with the program MOLMOL.
Figure 3 Comparison of images showing different prion strains stained with PTAA and Thioflavin T. (A) MDePrPSc, (B) OvPrPSc and (C) BoPrPSc prion deposits. PTAA-stained deposits appear in yellow-red. Scale bars represent 500 μm.
(Adapted from Sigurdson, C.J., Nilsson, K.P., Hornemann, S. et al. (2009). Proc. Natl Acad. Sci., U S A, 106, 304–309.)