title: Nucleic acid and prion protein interaction produces spherical amyloids which can function in vivo as coats of spongiform encephalopathy agent.
abstract: The infectious agent of transmissible spongiform encephalopathies (TSE) has been considered to be PrP(SC), a structural isoform of cellular prion protein PrP(C). PrP(SC) can exist as oligomers and/or as amyloid polymers. Nucleic acids induce structural conversion of recombinant prion protein PrP and PrP(C) to PrP(SC) form in solution and in vitro. Here, we report that nucleic acids, by interacting with PrP in solution, produce amyloid fibril and fibres of different morphologies, similar to those identified in the diseased brains. In addition, the same interaction produces polymer lattices and spherical amyloids of different dimensions (15-150 nm in diameters). The polymer lattices show apparent morphological similarity to the two-dimensional amyloid crystals obtained from linear amyloids isolated in vivo. The spherical amyloids structurally resemble "spherical particles" observed in natural spongiform encephalopathy (SE) and in scrapie-infected brains (TSE). We suggest that spherical amyloids, PrP(SC)-amylospheroids, are probable constituents of the coat of the spherical particles found in vivo and the latter can act as protective coats of the SE and TSE agents in vivo.
authors.affiliation: Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France. nandi@tours.inra.fr
authors.forename: P K
authors.initials: PK
authors.lastname: Nandi
authors.forename: J-C
authors.initials: JC
authors.lastname: Nicole
mesh_terms: D000682:Amyloid / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D051379:Mice; D008854:Microscopy, Electron; D009696:Nucleic Acids / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding
chemical_list: D000682:Amyloid; D009696:Nucleic Acids; D011328:Prions