In:
Journal of Virology, American Society for Microbiology, Vol. 75, No. 21 ( 2001-11), p. 10024-10032
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.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.75.21.10024-10032.2001
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2001
detail.hit.zdb_id:
1495529-5
Permalink