Paper Citing NAMD - Abstract
Charlet, L.; Chapron, Y.; Roman-Ross, G.; Hureau, C.; Hawkins, D. P.; Ragnarsdottir, K. V.
Prions, Metals, and Soils
ADSORPTION OF METALS BY GEOMEDIA II: VARIABLES, MECHANISMS, AND MODEL APPLICATIONS, 7:125-152, 2008
This study focused on understanding whether trace metals in the natural environment have a role to play in the development of prion diseases. The prion protein (PrP) is the key protein implicated in the development of scrapie, a sheep- and goat-specific transmissible spongiform encephalopathy. The N-terminal tail of the protein includes five copper chelating sites as well as numerous positively charged amino acids, which all may induce a binding of the protein to clay minerals, as shown, e. g., by molecular dynamics (MD) calculations and electron paramagnetic resonance (EPR) spectroscopy. The C-terminal part of the protein has a hydrophobic core that may also interact with low-charge clay surfaces as well as organic matter. The speciation of Cu-PrP chelates is show to change upon adsorption on clay minerals. Cu coordination at a given pH in the adsorbed state in presence of PrP is similar to Cu coordination in a solution of lower pH. This, together with high available Mn2+ concentrations, favors the exchange of Mn2+ for Cu2+, which is shown by MD to occur in three steps. Scrapie-prone farms in France, Iceland, and Italy were shown indeed to have soils with extremely high "easily reducible Mn" and pore waters with low free Cu2+ ion activity. In contrast, in Icelandic young andosols, the correlation between scrapie-free and scrapie-prone areas was not as clear-cut as far as copper and manganese is concerned. Copper was seen to be higher (and can be considered adequate) than in the scrapie areas in France. In all areas manganese is considered to be above toxicity thresholds for sheep.
