TY - JOUR
T1 - Characterization of the F198S prion protein mutation
T2 - Enhanced glycosylation and defective refolding
AU - Zaidi, Syed I.A.
AU - Richardson, Sandra L.
AU - Capellari, Sabina
AU - Song, Li
AU - Smith, Mark A.
AU - Ghetti, Bernardino
AU - Sy, Man Sun
AU - Gambetti, Pierluigi
AU - Petersen, Robert B.
PY - 2005
Y1 - 2005
N2 - 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.
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-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.
UR - http://www.scopus.com/inward/record.url?scp=17844375090&partnerID=8YFLogxK
U2 - 10.3233/JAD-2005-7209
DO - 10.3233/JAD-2005-7209
M3 - Article
C2 - 15851854
AN - SCOPUS:17844375090
VL - 7
SP - 159
EP - 171
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 2
ER -