V180I mutation of the prion protein gene associated with atypical PrPSc glycosylation

S Chasseigneaux, S Haïk, I Laffont-Proust… - Neuroscience …, 2006 - Elsevier
S Chasseigneaux, S Haïk, I Laffont-Proust, O De Marco, M Lenne, JP Brandel, JJ Hauw…
Neuroscience letters, 2006Elsevier
A valine to isoleucine mutation at residue 180 was identified in a French patient with
Creutzfeldt-Jakob disease (CJD). The mutation is located in the close vicinity of one of the
two N-glycosylation sites of the cellular prion protein (PrPC). Western blot analysis revealed
accumulation in the brain of the pathogenic proteinase K-resistant PrP (PrPSc) isoform with
the notable absence of the diglycosylated band. The mutant protein expressed in CHO cells
was correctly glycosylated, suggesting that the atypical glycosylation pattern of PrPSc was …
A valine to isoleucine mutation at residue 180 was identified in a French patient with Creutzfeldt-Jakob disease (CJD). The mutation is located in the close vicinity of one of the two N-glycosylation sites of the cellular prion protein (PrPC). Western blot analysis revealed accumulation in the brain of the pathogenic proteinase K-resistant PrP (PrPSc) isoform with the notable absence of the diglycosylated band. The mutant protein expressed in CHO cells was correctly glycosylated, suggesting that the atypical glycosylation pattern of PrPSc was not due to the mutation at position 180. These results suggest that the diglycosylated form of the mutant PrP180I prevents its conversion into the pathogenic mutant form PrPSc180I, supporting a central role of N-linked glycan chains in the PrP conversion process.
Elsevier