NR AJLA
AU Piccardo,P.; Liepnieks,J.J.; William,A.; Dlouhy,S.R.; Farlow,M.R.; Young,K.; Nochlin,D.; Bird,T.D.; Nixon,R.R.; Ball,M.J.; DeCarli,C.; Bugiani,O.; Tagliavini,F.; Benson,M.D.; Ghetti,B.
TI Prion proteins with different conformations accumulate in Gerstmann-Sträussler-Scheinker disease caused by A117V and F198S mutations
QU American Journal of Pathology 2001 Jun; 158(6): 2201-7
PT journal article
AB Gerstmann-Sträussler-Scheinker disease (GSS) is characterized by the accumulation of proteinase K (PK)-resistant prion protein fragments (PrPsc) of approximately 7 to 15 kd in the brain. Purified GSS amyloid is composed primarily of approximately 7-kd PrP peptides, whose N terminus corresponds to residues W(81) and G(88) to G(90) in patients with the A117V mutation and to residue W(81) in patients with the F198S mutation. The aim of this study was to characterize PrP in brain extracts, microsomal preparations, and purified fractions from A117V patients and to determine the N terminus of PrPsc species in both GSS A117V and F198S. In all GSS A117V patients, the approximately 7-kd PrPsc fragment isolated from nondigested and PK-digested samples had the major N terminus at residue G(88) and G(90), respectively. Conversely, in all patients with GSS F198S, an approximately 8-kd PrPsc fragment was isolated having the major N terminus start at residue G(74). It is possible that a further degradation of this fragment generates the amyloid subunit starting at W(81). The finding that patients with GSS A117V and F198S accumulate PrPsc fragments of different size and N-terminal sequence, suggests that these mutations generate two distinct PrP conformers.
MH Amyloid/*genetics; Binding Sites; Brain/metabolism; Cell Extracts/analysis; Endopeptidase K/chemistry; Gerstmann-Sträussler-Scheinker Disease/*genetics/metabolism; Glycosylation; Human; Peptide Fragments/chemistry; *Point Mutation; PrPsc Proteins/*chemistry/isolation & purification/metabolism; Protein Conformation; Protein Precursors/*genetics; Subcellular Fractions/metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Indiana Alzheimer Disease Center and the Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202-5120, USA. ppiccard@iupui.edu
SP englisch
PO USA