Synthetic prions generated in vitro are similar to a newly identified subpopulation of PrPScfrom sporadic Creutzfeldt-Jakob Disease

Bocharova, Olga V. and Breydo, Leonid and Salnikov, Vadim V. and Gill, Andrew and Baskakov, Ilia V. (2005) Synthetic prions generated in vitro are similar to a newly identified subpopulation of PrPScfrom sporadic Creutzfeldt-Jakob Disease. Protein Science, 14 (5). pp. 1222-1232. ISSN 1469-896X

Full content URL: https://onlinelibrary.wiley.com/doi/abs/10.1110/ps...

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Abstract

In recent studies, the amyloid form of recombinant prion protein (PrP) encompassing residues 89–230 (rPrP 89-230) produced in vitro induced transmissible prion disease in mice. These studies showed that unlike “classical” PrPSc produced in vivo, the amyloid fibrils generated in vitro were more proteinase-K sensitive. Here we demonstrate that the amyloid form contains a proteinase K-resistant core composed only of residues 152/153–230 and 162–230. The PK-resistant fragments of the amyloid form are similar to those observed upon PK digestion of a minor subpopulation of PrPSc recently identified in patients with sporadic Creutzfeldt-Jakob disease (CJD). Remarkably, this core is sufficient for self-propagating activity in vitro and preserves a β-sheet-rich fibrillar structure. Full-length recombinant PrP 23-230, however, generates two subpopulations of amyloid in vitro: One is similar to the minor subpopulation of PrPSc, and the other to classical PrPSc. Since no cellular factors or templates were used for generation of the amyloid fibrils in vitro, we speculate that formation of the subpopulation of PrPSc with a short PK-resistant C-terminal region reflects an intrinsic property of PrP rather than the influence of cellular environments and/or cofactors. Our work significantly increases our understanding of the biochemical nature of prion infectious agents and provides a fundamental insight into the mechanisms of prions biogenesis.

Keywords:prion protein, transmissible spongiform encephalopathies, creutzfeldt jakob disease
Subjects:B Subjects allied to Medicine > B140 Neuroscience
B Subjects allied to Medicine > B132 Pathobiology
C Biological Sciences > C760 Biomolecular Science
Divisions:College of Science
ID Code:29565
Deposited On:30 Aug 2018 10:15

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