The Thr183Ala Mutation, Not the Loss of the First Glycosylation Site, Alters the Physical Properties of the Prion Protein

Article type: Research Article

Authors: Capellari, Sabina | Zaidi, Syed I.A. | Long, Amy C. | Kwon, Eunice E. | Petersen, Robert B.^{; *}

Affiliations: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106-2622, USA

Correspondence: [*] Corresponding author: Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106-2622, USA, E-mail: [email protected]

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.

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DOI: 10.3233/JAD-2000-2104

Journal: Journal of Alzheimer's Disease, vol. 2, no. 1, pp. 27-35, 2000