Manganese Binding

Interaction between PrP and other metals has also been studied but to a lesser degree (Figure 4). In addition to metal binding it has also been suggested that interactions between metals can also increase the aggregation and conformational change of PrP. In particular, it has been suggested that copper and manganese can accelerate the formation of aggregated, protease resistant protein [41,100-102].

SMB Cells

Infected Control

Figure 4. PrPSc binds manganese. Metal affinity chromatography using a manganese-charged column was used to isolate manganese binding proteins from cultured cells. The cells used were either cells without scrapie infection or scrapie-infected cells (SMB). The bound proteins were eluted and then analyzed by western blot. In both cases PrP from the cells bound to the column. In the case of the infected cells protease resistant PrP also bound to the column. PrPSc is resistant to protease K (PK) treatment (200 |xg/mL, 3h). This result shows that PrPSc can be isolated by its affinity for manganese.

Figure 4. PrPSc binds manganese. Metal affinity chromatography using a manganese-charged column was used to isolate manganese binding proteins from cultured cells. The cells used were either cells without scrapie infection or scrapie-infected cells (SMB). The bound proteins were eluted and then analyzed by western blot. In both cases PrP from the cells bound to the column. In the case of the infected cells protease resistant PrP also bound to the column. PrPSc is resistant to protease K (PK) treatment (200 |xg/mL, 3h). This result shows that PrPSc can be isolated by its affinity for manganese.

Metals have a high potential to interact with p-sheet structural elements and therefore have the potential to exacerbate aggregation. It was found that copper has the potential to enhance the infective potency of scrapie infection [103]. In contrast, treatment with penicillamine, a copper chelator, lengthens the incubation period of scrapie, indicating a protective effect [104]. It has been found that hydrogen peroxide causes oxidation of methionine residues in PrP [105]. In addition, hydrogen peroxide can cause the cleavage of PrP at an alternative site in the presence of copper [106], but hydrogen peroxide can also be generated when PrP or fragments of PrP interact with metal such as copper and iron [107]. These data indicate that interactions between PrP and metals need not be beneficial (Figure 5).

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