NR AMEQ
AU Walmsley,A.R.; Hooper,N.M.
TI Distance of sequons to the C-terminus influences the cellular N-glycosylation of the prion protein
QU Biochemical Journal 2003; 370: 351-355
PT journal article
AB Cell-specific differences in the utilisation of the two N-glycosylation sequons (Asn180-Ile-Thr and Asn196-Phe-Thr) of the prion protein (PrP) has been proposed to influence the etiology of the neurodegenerative prion diseases. As the N-glycosylation of PrP is ablated by deletion of the C-terminal glycosyl-phosphatidylinositol (GPI) anchor signal sequence, we have investigated the determinants for PrP sequon utilisation in human neuronal cells using the novel approach of restoring N-glycosylation to secreted forms of PrP lacking a GPI anchor. N-glycosylation was restored to an efficiency comparable with that of GPI anchored PrP when the distance of the sequon to the C-terminus was increased such that it was sufficient to reach the active site of oligosaccharide transferase prior to chain termination. Our findings indicate that sequon utilisation in PrP is a co-translational process that precedes GPI anchor addition and, as such, will be greatly influenced by the dynamics of the translocon-oligosaccharide transferase complex.
SP englisch