| First Author | Oliveira-Martins JB | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 2 | Pages | e9107 |
| PubMed ID | 20161712 | Mgi Jnum | J:157999 |
| Mgi Id | MGI:4437506 | Doi | 10.1371/journal.pone.0009107 |
| Citation | Oliveira-Martins JB, et al. (2010) Unexpected tolerance of alpha-cleavage of the prion protein to sequence variations. PLoS One 5(2):e9107 |
| abstractText | The cellular form of the prion protein, PrP(C), undergoes extensive proteolysis at the alpha site (109K [see text]H110). Expression of non-cleavable PrP(C) mutants in transgenic mice correlates with neurotoxicity, suggesting that alpha-cleavage is important for PrP(C) physiology. To gain insights into the mechanisms of alpha-cleavage, we generated a library of PrP(C) mutants with mutations in the region neighbouring the alpha-cleavage site. The prevalence of C1, the carboxy adduct of alpha-cleavage, was determined for each mutant. In cell lines of disparate origin, C1 prevalence was unaffected by variations in charge and hydrophobicity of the region neighbouring the alpha-cleavage site, and by substitutions of the residues in the palindrome that flanks this site. Instead, alpha-cleavage was size-dependently impaired by deletions within the domain 106-119. Almost no cleavage was observed upon full deletion of this domain. These results suggest that alpha-cleavage is executed by an alpha-PrPase whose activity, despite surprisingly limited sequence specificity, is dependent on the size of the central region of PrP(C). |
