A physiological role for healthy prions
30 May 2006
Researchers in Germany have shown that the healthy version of the scrapie pathogen helps maintain the optimum concentration of copper ions in the cell. The researchers note that an excess of manganese over copper is linked to the misfolding process that converts the copper regulating prion protein into the infectious agent.
Gerd Multhaup and colleagues at the Free University of Berlin engineered yeast cells to produce sheep prion proteins. They studied the response of the cultured cells to variations of metal ion concentrations.
When prion-producing yeast cells, but not normal yeast cells, were grown at low copper concentrations, the cells became enriched in copper ions. This suggests that the prions might facilitate copper uptake or even act as ion channels for copper itself, say the researchers.
At unusually high copper concentrations, the presence of prions limited the increase of the intracellular copper-ion concentration, suggesting that it may act as a buffer to regulate copper concentrations.
Nigel Robinson of the University of Newcastle, UK, commented: 'Copper is prone to bind tightly to the wrong proteins. These data support the notion that [prion proteins] have a role in the cellular handling of copper, rather than solely binding copper as a pathological aberration.'
The researchers also investigated the effect of metal ions on the conversion of healthy prions in yeast cells to protease-resistant forms, which have been linked to prion diseases, such as scrapie and bovine spongiform encephalopathy. Previous studies of the protein in solution had established no such effect, but this work using yeast cells showed that an excess of manganese over copper ions makes the prions misfold into the protease-resistant form.
C Treiber et al, Biochemistry 2006, DOI 10.1021/bi060244h