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 journalArticle

17 Citations (Scopus)

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 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 (US)
Pages (from-to)159-171
Number of pages13
JournalJournal of Alzheimer's Disease
Volume7
Issue number2
DOIs
StatePublished - Jan 1 2005

Fingerprint

Prion Diseases
Gerstmann-Straussler-Scheinker Disease
Glycosylation
Mutant Proteins
Mutation
PrPSc Proteins
Amyloid Plaques
Point Mutation
Peptide Hydrolases
Infection
Prion Proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Zaidi, S. I. A., Richardson, S. L., Capellari, S., Song, L., Smith, M. A., Ghetti, B., ... Petersen, R. B. (2005). Characterization of the F198S prion protein mutation: Enhanced glycosylation and defective refolding. Journal of Alzheimer's Disease, 7(2), 159-171. https://doi.org/10.3233/JAD-2005-7209

Characterization of the F198S prion protein mutation : Enhanced glycosylation and defective refolding. / Zaidi, Syed I.A.; Richardson, Sandra L.; Capellari, Sabina; Song, Li; Smith, Mark A.; Ghetti, Bernardino; Sy, Man Sun; Gambetti, Pierluigi; Petersen, Robert B.

In: Journal of Alzheimer's Disease, Vol. 7, No. 2, 01.01.2005, p. 159-171.

Research output: Contribution to journalArticle

Zaidi, SIA, Richardson, SL, Capellari, S, Song, L, Smith, MA, Ghetti, B, Sy, MS, Gambetti, P & Petersen, RB 2005, 'Characterization of the F198S prion protein mutation: Enhanced glycosylation and defective refolding', Journal of Alzheimer's Disease, vol. 7, no. 2, pp. 159-171. https://doi.org/10.3233/JAD-2005-7209
Zaidi, Syed I.A. ; Richardson, Sandra L. ; Capellari, Sabina ; Song, Li ; Smith, Mark A. ; Ghetti, Bernardino ; Sy, Man Sun ; Gambetti, Pierluigi ; Petersen, Robert B. / Characterization of the F198S prion protein mutation : Enhanced glycosylation and defective refolding. In: Journal of Alzheimer's Disease. 2005 ; Vol. 7, No. 2. pp. 159-171.
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