title: Why don't humans get scrapie from eating sheep? A possible explanation based on secondary structure predictions.
abstract: In an effort to find a structural explanation for the lack of direct transmission of scrapie from sheep to humans, secondary structure predictions are used to locate the segments of the prion sequence which may be involved in the transformation from the normal form of the prion protein, which has high helix content, to the pathogenic form, which has high beta-sheet content. The Chou-Fasman algorithm, which calculates propensities for both helix and sheet formation, was used to predict the secondary structures of the scrapie-resistant and the scrapie-susceptible variants of the ovine prion protein. The scrapie-susceptible variant, which has a glutamine at residue position 168 (human prion protein numbering), is predicted to have a propensity for sheet formation in that region of the molecule, while the scrapie-resistant variant, which has an arginine at position 168, does not. The valine at position 133, additionally present in the ovine variant which is the most susceptible to scrapie, is predicted to result in even more sheet formation. When the predicted secondary structure of the human prion protein is compared to those of the ovine prion protein variants, the human protein is found to be most similar to the scrapie-resistant variant. This result is proposed to provide a possible explanation for the observation that scrapie is not directly transmitted from sheep to humans.
authors.affiliation: Marine Science Institute, College of Science, University of the Philippines Diliman, Quezon City 1101, Philippines.
authors.forename: G P
authors.initials: GP
authors.lastname: Concepcion
authors.forename: M P C
authors.initials: MP
authors.lastname: David
authors.forename: E A
authors.initials: EA
authors.lastname: Padlan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008461:Meat Products; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012608:Scrapie / Q000635:transmission*; D017386:Sequence Homology, Amino Acid; D012756:Sheep
chemical_list: D011328:Prions