NR AHPX
AU Ma,J.; Lindquist,S.L.
TI Conversion of PrP to a Self-Perpetuating PrPsc-like Conformation in the Cytosol
QU Science 2002 Nov 29; 298(5599): 1785-8
PT journal article
AB A rare conformation of the prion protein, PrPsc, is found only in mammals with transmissible prion diseases and represents either the infectious agent itself or a major component of it. The mechanism for initiating PrPsc formation is unknown. We report that PrP retrogradely transported out of the endoplasmic reticulum produced both amorphous aggregates and a PrPsc-like conformation in the cytosol. The distribution between these forms correlated with the rate of appearance in the cytosol. Once conversion to the PrPsc-like conformation occurred, it was sustained. Thus, PrP has an inherent capacity to promote its own conformational conversion in mammalian cells. These observations might explain the origin of PrPsc.
AD Howard Hughes Medical Institute (HHMI), University of Chicago, Chicago, IL 60637, USA., Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
SP englisch
PO USA
EA pdf-Datei und Supplement