Molecular basis of scrapie strain glycoform variation.

Abstract

Transmissible spongiform encephalopathies (TSE) are characterized by the conversion of a protease-sensitive host glycoprotein, prion protein or PrP-sen, to a protease-resistant form (PrP-res). PrP-res molecules that accumulate in the brain and lymphoreticular system of the host consist of three differentially glycosylated forms. Analysis of the relative amounts of the PrP-res glycoforms has been used to discriminate TSE strains and has become increasingly important in the differential diagnosis of human TSEs. However, the molecular basis of PrP-res glycoform variation between different TSE agents is unknown. Here we report that PrP-res itself can dictate strain-specific PrP-res glycoforms. The final PrP-res glycoform pattern, however, can be influenced by the cell and significantly altered by subtle changes in the glycosylation state of PrP-sen. Thus, strain-specific PrP-res glycosylation profiles are likely the consequence of a complex interaction between PrP-res, PrP-sen, and the cell and may indicate the cellular compartment in which the strain-specific formation of PrP-res occurs.

• Authors: Ina Vorberg, Suzette A Priola
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 39 Pg. 36775-81 (Sep 27 2002) ISSN: 0021-9258 [Print] United States
• PMID: 12138171 (Publication Type: Journal Article)

Chemical References

• PrPSc Proteins

Topics

• Animals
• Blotting, Western
• Brain (metabolism)
• Cell-Free System
• Glycosylation
• Humans
• Mice
• Phenotype
• PrPSc Proteins (chemistry, metabolism)
• Prion Diseases (metabolism)
• Scrapie (metabolism)
• Tumor Cells, Cultured