NR AJPG
AU Priola,S.A.; Lawson,V.A.
TI Glycosylation influences cross-species formation of protease-resistant prion protein
QU EMBO Journal 2001 Dec 3; 20(23): 6692-9
PT journal article
AB A key event in the transmissible spongiform encephalopathies (TSEs) is the formation of aggregated and protease-resistant prion protein, PrPres, from a normally soluble, protease-sensitive and glycosylated precursor, PrP-sen. While amino acid sequence similarity between PrP-sen and PrPres influences both PrPres formation and cross-species transmission of infectivity, the influence of co- or post-translational modifications to PrP-sen is unknown. Here we report that, if PrP-sen and PrPres are derived from different species, PrP-sen glycosylation can significantly affect PrPres formation. Glycosylation affected PrPres formation by influencing the amount of PrP-sen bound to PrPres, while the amino acid sequence of PrP-sen influenced the amount of PrPres generated in the post-binding conversion step. Our results show that in addition to amino acid sequence, co- or post-translational modifications to PrP-sen influence PrPres formation in vitro. In vivo, these modifications might contribute to the resistance to infection associated with transmission of TSE infectivity across species barriers.
MH Animal; Antibiotics/pharmacology; Antiviral Agents/pharmacology; Cell-Free System; Cloning, Molecular; Dose-Response Relationship, Drug; Endopeptidases/*metabolism; Epitopes; *Glycosylation; Hamsters; Mice; PrPc Proteins/*metabolism; PrPsc Proteins/*metabolism; Precipitin Tests; Prion Diseases/transmission; Prions/*metabolism; Protein Binding; Protein Processing, Post-Translational; Recombinant Proteins/metabolism/pharmacology; Species Specificity; Tunicamycin/pharmacology
AD Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. spriola@nih.gov
SP englisch
PO England