NR ASUM
AU Zaidi,S.I.A.; Richardson,S.L.; Capellari,S.; Song,L.; Smith,M.A.; Ghetti,B.; Sy,M.S.; Gambetti,P.; Petersen,R.B.
TI Characterization of the F198S prion protein mutation: enhanced glycosylation and defective refolding.
QU Journal of Alzheimer's Disease : JAD 2005 Apr; 7(2): 159-71; discussion 173-80
PT journal article
AB 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-Sträussler-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.
MH Amyloid/genetics; Binding Sites; Brain/metabolism; Cell Extracts; DNA Mutational Analysis; DNA Primers/genetics; Endopeptidase K/metabolism; Gerstmann-Sträussler-Scheinker Disease/*genetics/metabolism; *Glycosylation; Humans; Immunoprecipitation; Point Mutation/*genetics; PrPsc Proteins/*metabolism; Prions/*genetics; Protein Conformation; Protein Folding; Protein Precursors/metabolism; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.; Subcellular Fractions/metabolism
AD Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC 20059, USA
SP englisch
PO Niederlande