NR AHPZ
AU Ma,J.; Lindquist,S.L.
TI De novo generation of a PrPsc-like conformation in living cells
QU Nature Cell Biology 1999 Oct; 1(6): 358-61
PT journal article
AB Conformational conversion of the cellular PrPc protein to PrPsc is a central aspect of the prion diseases, but how PrP initially converts to this conformation remains a mystery. Here we show that PrP expressed in the yeast cytoplasm, instead of the endoplasmic reticulum, acquires the characteristics of PrPsc, namely detergent insolubility and a distinct pattern of protease resistance. Neuroblastoma cells cultured under reducing, glycosylation-inhibiting conditions produce PrP with the same characteristics. We therefore describe what is, to our knowledge, the first conversion of full-length PrP in a heterologous system, show the importance of reducing and deglycosylation conditions in PrP conformational transitions, and suggest a model for initiating events in sporadic and inherited prion diseases.
MH Animal; Cytoplasm/metabolism; Cytosol/metabolism; Endopeptidase K/metabolism; Gene Expression; Mice; Neuroblastoma; PrPsc Proteins/*biosynthesis/chemistry; Prions/genetics; Protein Conformation; Saccharomyces cerevisiae; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured; Two-Hybrid System Techniques
AD Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, 5841 S. Maryland Avenue MC1028, Chicago, Illinois 60637, USA
SP englisch
PO England