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Low density subcellular fractions enhance disease-specific prion protein misfolding
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Graham, James F., Agarwal, Sonya, Kurian, Dominic, Kirby, Louise, Pinheiro, Teresa J. T. and Gill, Andrew C. (2010) Low density subcellular fractions enhance disease-specific prion protein misfolding. Journal of Biological Chemistry, Vol.285 (No.13). pp. 9868-9880. doi:10.1074/jbc.M109.093484 ISSN 0021-9258.
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Official URL: http://dx.doi.org/10.1074/jbc.M109.093484
Abstract
The production of prion particles in vitro by amplification with or without exogenous seed typically results in infectivity titers less than those associated with PrPSc isolated ex vivo and highlights the potential role of co-factors that can catalyze disease-specific prion protein misfolding in vivo. We used a cell-free conversion assay previously shown to replicate many aspects of transmissible spongiform encephalopathy disease to investigate the cellular location of disease-specific co-factors using fractions derived from gradient centrifugation of a scrapie-susceptible cell line. Fractions from the low density region of the gradient doubled the efficiency of conversion of recombinant PrP. These fractions contain plasma membrane and cytoplasmic proteins, and conversion enhancement can be achieved using PrPSc derived from two different strains of mouse-passaged scrapie as seed. Equivalent fractions from a second scrapie-susceptible cell line also stimulate conversion. We also show that subcellular fractions enhancing disease-specific prion protein conversion prevent in vitro fibrillization of recombinant prion protein, suggesting the existence of separate, competing mechanisms of disease-specific and nonspecific misfolding in vivo.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QD Chemistry | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010) | ||||
Journal or Publication Title: | Journal of Biological Chemistry | ||||
Publisher: | American Society for Biochemistry and Molecular Biology | ||||
ISSN: | 0021-9258 | ||||
Official Date: | 26 March 2010 | ||||
Dates: |
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Volume: | Vol.285 | ||||
Number: | No.13 | ||||
Number of Pages: | 13 | ||||
Page Range: | pp. 9868-9880 | ||||
DOI: | 10.1074/jbc.M109.093484 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Great Britain. Dept. for Environment, Food & Rural Affairs (DEFRA) |
Data sourced from Thomson Reuters' Web of Knowledge
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