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journal article Nov 01, 2001

Deletion of β-Strand and α-Helix Secondary Structure in Normal Prion Protein Inhibits Formation of Its Protease-Resistant Isoform

Ina Vorberg Kaman Chan Suzette A. Priola
Journal of Virology Vol. 75 No. 21 pp. 10024-10032 · American Society for Microbiology
View at Publisher Save 10.1128/jvi.75.21.10024-10032.2001
Abstract
ABSTRACT

A fundamental event in the pathogenesis of transmissible spongiform encephalopathies (TSE) is the conversion of a normal, proteinase K-sensitive, host-encoded protein, PrP-sen, into its protease-resistant isoform, PrP-res. During the formation of PrP-res, PrP-sen undergoes conformational changes that involve an increase of β-sheet secondary structure. While previous studies in which PrP-sen deletion mutants were expressed in transgenic mice or scrapie-infected cell cultures have identified regions in PrP-sen that are important in the formation of PrP-res, the exact role of PrP-sen secondary structures in the conformational transition of PrP-sen to PrP-res has not yet been defined. We constructed PrP-sen mutants with deletions of the first β-strand, the second β-strand, or the first α-helix and tested whether these mutants could be converted to PrP-res in both scrapie-infected neuroblastoma cells (Sc
+
-MNB cells) and a cell-free conversion assay. Removal of the second β-strand or the first α-helix significantly altered both processing and the cellular localization of PrP-sen, while deletion of the first β-strand had no effect on these events. However, all of the mutants significantly inhibited the formation of PrP-res in Sc
+
-MNB cells and had a greatly reduced ability to form protease-resistant PrP in a cell-free assay system. Thus, our results demonstrate that deletion of the β-strands and the first α-helix of PrP-sen can fundamentally affect PrP-res formation and/or PrP-sen processing.
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References
67
[5]
Caughey B. Formation of protease-resistant prion protein in cell-free systems Prions: molecular and cellular biology. Harris D. A. 1999 27 44 Horizon Scientific Wymondham United Kingdom
[13]
Chesebro B. Wehrly K. Caughey B. Nishio J. Ernst D. Race R. Foreign PrP expression and scrapie infection in tissue culture cell lines.Dev. Biol. Stand. 80 1993 131 140
[32]
Lawson V. A. S. A. Priola K. Wehrly and B. Chesebro. N-terminal truncation of prion protein affects both formation and conformation of abnormal protease-resistant prion protein generated in vitro . J. Biol. Chem. in press.
[35]
McKinley M. P. Taraboulos A. Kenaga L. Serban D. Stieber A. DeArmond S. J. Prusiner S. B. Gonatas N. Ultrastructural localization of scrapie prion proteins in cytoplasmic vesicles of infected cultured cells.Lab. Investig. 65 1991 622 630

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67
References
Details
Published
Nov 01, 2001
Vol/Issue
75(21)
Pages
10024-10032
License
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Authors
I
Ina Vorberg

<!--label omitted: 1-->Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,1 and

K
Kaman Chan

<!--label omitted: 2-->Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 943052

S
Suzette A. Priola

<!--label omitted: 1-->Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,1 and

Cite This Article
Ina Vorberg, Kaman Chan, Suzette A. Priola (2001). Deletion of β-Strand and α-Helix Secondary Structure in Normal Prion Protein Inhibits Formation of Its Protease-Resistant Isoform. Journal of Virology, 75(21), 10024-10032. https://doi.org/10.1128/jvi.75.21.10024-10032.2001
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