title: Fibril formation of the rabbit/human/bovine prion proteins.
abstract: Prion diseases are infectious fatal neurodegenerative diseases including Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. The misfolding and conversion of cellular PrP in such mammals into pathogenic PrP is believed to be the key procedure. Rabbits are among the few mammalian species that exhibit resistance to prion diseases, but little is known about the molecular mechanism underlying such resistance. Here, we report that the crowding agents Ficoll 70 and dextran 70 have different effects on fibrillization of the recombinant full-length PrPs from different species: although these agents dramatically promote fibril formation of the proteins from human and cow, they significantly inhibit fibrillization of the rabbit protein by stabilizing its native state. We also find that fibrils formed by the rabbit protein contain less β-sheet structure and more α-helix structure than those formed by the proteins from human and cow. In addition, amyloid fibrils formed by the rabbit protein do not generate a proteinase K-resistant fragment of 15-16-kDa, but those formed by the proteins from human and cow generate such proteinase K-resistant fragments. Together, these results suggest that the strong inhibition of fibrillization of the rabbit PrP by the crowded physiological environment and the absence of such a protease-resistant fragment for the rabbit protein could be two of the reasons why rabbits are resistant to prion diseases.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xu
authors.initials: X
authors.lastname: Yan
authors.forename: Kai
authors.initials: K
authors.lastname: Pan
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Zheng-Sheng
authors.initials: ZS
authors.lastname: Xie
authors.forename: Geng-Fu
authors.initials: GF
authors.lastname: Xiao
authors.forename: Fu-Quan
authors.initials: FQ
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
mesh_terms: D000818:Animals; D002417:Cattle; D019286:Endopeptidase K / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D059748:Proteolysis; D057165:Proteostasis Deficiencies / Q000378:metabolism; D011817:Rabbits; D013045:Species Specificity
chemical_list: D011328:Prions; D019286:Endopeptidase K