Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-33110
Oliveira-Martins, J B; Yusa, S I; Calella, A M; Bridel, C; Baumann, F; Dametto, P; Aguzzi, A (2010). Unexpected tolerance of alpha-cleavage of the prion protein to sequence variations. PLoS ONE, 5(2):e9107.
View at publisher
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).
42 downloads since deposited on 26 Mar 2010
11 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology|
|Dewey Decimal Classification:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||26 Mar 2010 09:59|
|Last Modified:||12 Nov 2014 12:24|
|Publisher:||Public Library of Science (PLoS)|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page