Figures & data
Figure 1 Spontaneous inward currents induced by expression of ΔCR PrP in HEK cells. HEK cells expressing vector, WT PrP, ΔCR PrP or ΔCR + WT PrP were analyzed by whole-cell patch-clamping. Recordings were made at a holding potential of −80 mV. Spontaneous current activity was observed only in cells expressing ΔCR PrP, and was suppressed by co-expression of WT PrP.
Figure 2 Schematic of murine PrP showing domain structure and mutations. ER signal sequence (SS, blue, aa 1–22); polybasic domain (yellow, aa 23–31); octapeptide repeats (OR, magenta, aa 51–90); charge cluster (CC, red, aa 94–110); hydrophobic domain (HD, green, aa 111–134); GPI signal sequence (GPI, purple, 231–254). Three α helices (H1, H2 and H3), two N-linked oligosaccharides (hexagons), and one disulfide bond (S-S) are present in the C-terminal half of PrP. The sequences for amino acids 23–31 and 94–134 are shown above the schematic. The boxed residues (105–125) indicate those deleted in ΔCR PrP. Residues mutated in familial prion diseases are indicated in red, and a nonpathogenic polymorphism in blue, with arrows pointing to the substituted amino acid.
Figure 3 Ion Channel Formation Model of PrP-dependent toxicity. (A) ΔCR PrP, as a result of deletion of amino acids 105–125 (red), creates channels or pores in the plasma membrane by insertion of N-terminal, polybasic region (residues 23–31, shown in yellow). This allows cations (purple balls) to permeate the plasma membrane. The presence of WT PrP closes the channel. (B) PrPSc (orange) or oligomers of the Aβ peptide (red) bind to PrPC and induce a ΔCR-like conformational change, resulting in transient pore formation and toxicity.
Table 1 Summary of structure-function study