Title : The Thr183Ala Mutation,
Not the Loss of the First Glycosylation Site, Alters the Physical Properties of the
Prion Protein
Abstract :
- The abnormal form of the prion protein has increased resistance to protease digestion and is insoluble in non-ionic detergents
- The normal prion protein is modified by the non-obligatory addition of two N-linked glycans
- One pathogenic mutation, Thr to Ala at residue 183 of the human prion protein , blocks addition of the first glycan to the Asp residue 181
- This mutation has been reported to result in intracellular retention of the mutant protein and its acquisition of pathogenic properties, presumably due to the lack of the glycan
- We report that the lack of the N-linked glycan at residue 181 is not responsible for the block in transport or the acquisition of pathogen-like properties, rather, the Thr to Ala mutation is itself the probable cause of the pathogenic phenotype