title: Characterization of the F198S prion protein mutation: enhanced glycosylation and defective refolding.
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.
authors.affiliation: Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC 20059, USA.
authors.forename: Syed I A
authors.initials: SI
authors.lastname: Zaidi
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Richardson
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Man-Sun
authors.initials: MS
authors.lastname: Sy
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
authors.forename: Robert B
authors.initials: RB
authors.lastname: Petersen
mesh_terms: D000682:Amyloid / Q000235:genetics; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002457:Cell Extracts; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D019286:Endopeptidase K / Q000378:metabolism; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D047468:Immunoprecipitation; D017354:Point Mutation / Q000235:genetics*; D018620:PrPSc Proteins / Q000378:metabolism*; D011328:Prions / Q000235:genetics*; D011487:Protein Conformation; D017510:Protein Folding; D011498:Protein Precursors / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000682:Amyloid; D002457:Cell Extracts; D017931:DNA Primers; D018620:PrPSc Proteins; D011328:Prions; D011498:Protein Precursors; D019286:Endopeptidase K