title: Generic amyloidogenicity of mammalian prion proteins from species susceptible and resistant to prions.
abstract: Prion diseases are lethal, infectious diseases associated with prion protein (PrP) misfolding. A large number of mammals are susceptible to both sporadic and acquired prion diseases. Although PrP is highly conserved and ubiquitously expressed in all mammals, not all species exhibit prion disease. By employing full length recombinant PrP from five known prion susceptible species (human, cattle, cat, mouse and hamster) and two species considered to be prion resistant (pig and dog) the amyloidogenicity of these PrPs has been delineated. All the mammalian PrPs, even from resistant species, were swiftly converted from the native state to amyloid-like structure when subjected to a native condition conversion assay. The PrPs displayed amyloidotypic tinctorial and ultrastructural hallmarks. Self-seeded conversion of the PrPs displayed significantly decreased lag phases demonstrating that nucleation dependent polymerization is a dominating mechanism in the fibrillation process. Fibrils from Aβ1-40, Aβ1-42, Lysozyme, Insulin and Transthyretin did not accelerate conversion of HuPrP whereas fibrils from HuPrP90-231 and HuPrP121-231 as well as full length PrPs of all PrPs efficiently seeded conversion showing specificity of the assay requiring the C-terminal PrP sequence. Our findings have implications for PrP misfolding and could have ramifications in the context of prion resistant species and silent carriers.
authors.affiliation: IFM-Department of Chemistry, Linköping University, SE-581 83 Linköping, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Nyström
authors.affiliation: IFM-Department of Chemistry, Linköping University, SE-581 83 Linköping, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Hammarström
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D052160:Benzothiazoles; D002942:Circular Dichroism; D006801:Humans; D007700:Kinetics; D008322:Mammals / Q000378:metabolism*; D008969:Molecular Sequence Data; D016624:Negative Staining; D011328:Prions / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure; D066329:Protein Aggregates; D017510:Protein Folding; D013045:Species Specificity; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D011328:Prions; D066329:Protein Aggregates; D013844:Thiazoles; C009462:thioflavin T