Characterization of the F198S prion protein mutation: Enhanced glycosylation and defective refolding

Syed I.A. Zaidi, Sandra L. Richardson, Sabina Capellari, Li Song, Mark A. Smith, Bernardino Ghetti, Man Sun Sy, Pierluigi Gambetti, Robert B. Petersen

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Prion diseases are associated with the accumulation of a misfolded, protease resistant form of the prion protein, PrPres. In humans there are a variety of different prion related diseases that are sporadic, inherited, or acquired by infection. Gerstmann-Straussler-Sheinker syndrome (GSS) is an inherited prion disease in which PrP^{res} accumulates as amorphous aggregates as well as in amyloid plaques. GSS has been associated with a variety of point mutations in the prion protein: 102, 105, 117, 131, 145, 187, 198, 202, 212, 217, and 232. The F198S mutation was discovered in a large Indiana kindred. Previous studies in vitro have shown that the 198 mutation results in structural instability of the prion protein. In the current study, we demonstrate in a cell model that the F198S mutant protein can be folded properly in a cellular context, but is unable to refold to a native state after denaturation. Further, the F198S mutation significantly affects glycosylation of the mutant protein.

Original languageEnglish
Pages (from-to)159-171
Number of pages13
JournalJournal of Alzheimer's Disease
Issue number2
StatePublished - 2005


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