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Updated: Aug 18, 2026

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Characterization of the F198S prion protein mutation: enhanced glycosylation and defective refolding
Syed I A Zaidi1, Sandra L Richardson, Sabina Capellari
1Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC 20059, USA.
Abstract:
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 PrPres 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.
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