Modelling charge interactions in the prion protein: predictions for pathogenesis.
Calculations are presented for the pH-dependence of stability and membrane charge complementarity of prion protein fragments. The theoretical results are compared with reported characterisations of prion protein folding in vitro. Discussion of models for conformational change and pathogenesis in vivo leads to the prediction of amino acids that could mediate sensitivity to the endosomal pH and to a design strategy for recombinant prion proteins with an increased susceptibility to prion proteinSc-like properties in vitro. In this model, the protective effect of certain basic polymorphisms can be interpreted in terms of oligomerisation on a negatively-charged surface.
Warwicker
J
J
Institute of Food Research, Reading Laboratory, UK. james.warwicker@bbsrc.ac.uk
D000818:Animals; D016208:Databases, Factual; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D017096:Prion Diseases / Q000209:etiology; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012756:Sheep; D055672:Static Electricity
D010446:Peptide Fragments; D011328:Prions