NR AMHI
AU Wegner,C.; Römer,A.; Schmalzbauer,R.; Lorenz,H.; Windl,O.; Kretzschmar,H.A.
TI Mutant prion protein acquires resistance to protease in mouse neuroblastoma cells
QU Journal of General Virology 2002 May; 83(5): 1237-45
PT journal article
AB Conversion of the cellular isoform of the prion protein (PrPc) into the pathogenic isoform (PrPsc) is thought to be the causative event in prion diseases. Biochemically, PrPsc differs from PrPc in its partial resistance to proteinase K (PK). The amino acid sequence AGAAAAGA, comprising residues 112-119 of the murine PrPc, has been shown to be amyloidogenic and evolutionarily conserved. To assess the effect of mutations at and around this hydrophobic sequence on protease resistance, the sequence was replaced either by alanines or by glycines and, in a third mutant, a large part surrounding this region was removed. The PrP mutant carrying substitutions of glycines for alanines showed PK resistance and aberrant proteolytic processing. Tetracycline-induced expression of this mutant indicated that resistance to protease is acquired concurrent with the synthesis of the protein. These findings indicate that mutations in the central hydrophobic region lead to immediate alterations in PrP structure and processing.
MH Animal; Doxycycline/pharmacology; Endopeptidases/*metabolism; Glycosylation; Hamsters; Mice; Mutation; Neuroblastoma/*metabolism; Prions/chemistry/*metabolism; Protein Conformation; Support, Non-U.S. Gov't
AD Institut für Neuropathologie, Universität Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, Germany.
SP englisch
PO England