N-terminal truncation of prion protein affects both formation and conformation of abnormal protease-resistant prion protein generated in vitro.
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| Abstract |
Transmissible spongiform encephalopathy diseases are characterized by conversion of the normal protease-sensitive host prion protein, PrP-sen, to an abnormal protease-resistant form, PrP-res. In the current study, deletions were introduced into the flexible tail of PrP-sen (23) to determine if this region was required for formation of PrP-res in a cell-free assay. PrP-res formation was significantly reduced by deletion of residues 34-94 relative to full-length hamster PrP. Deletion of another nineteen amino acids to residue 113 further reduced the amount of PrP-res formed. Furthermore, the presence of additional proteinase K cleavage sites indicated that deletion to residue 113 generated a protease-resistant product with an altered conformation. Conversion of PrP deletion mutants was also affected by post-translational modifications to PrP-sen. Conversion of unglycosylated PrP-sen appeared to alter both the amount and the conformation of protease-resistant PrP-res produced from N-terminally truncated PrP-sen. The N-terminal region also affected the ability of hamster PrP to block mouse PrP-res formation in scrapie-infected mouse neuroblastoma cells. Thus, regions within the flexible N-terminal tail of PrP influenced interactions required for both generating and disrupting PrP-res formation.
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| Authors | V A Lawson, S A Priola, K Wehrly, B Chesebro |
| Journal | The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 38 Pg. 35265-71 (Sep 21 2001) ISSN: 0021-9258 [Print] United States |
| PMID | 11466311 (Publication Type: Journal Article) |
| Chemical References |
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