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.
|Creative Commons: Attribution 3.0|
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).
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology|
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||26 Mar 2010 10:59|
|Last Modified:||28 Nov 2013 01:21|
|Publisher:||Public Library of Science|
|Citations:||Web of Science®. Times cited: 12|
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