NR AMOS
AU Wille,H.; Prusiner,S.B.; Cohen,F.E.
TI Scrapie infectivity is independent of amyloid staining properties of the N-terminally truncated prion protein
QU Journal of Structural Biology 2000 Jun; 130(2-3): 323-38
PT journal article
AB The prion protein undergoes a profound conformational change when the cellular isoform (PrPc) is converted into the disease-causing form (PrPsc). Limited proteolysis of PrPsc produces PrP 27-30, which readily polymerizes into amyloid. To study the relationship between PrP amyloid and infectivity, we employed organic solvents that perturb protein conformation. Hexafluoro-2-propanol (HFIP), which promotes alpha-helix formation, modified the ultrastructure of PrP amyloid and decreased the beta-sheet content as well as prion infectivity. HFIP reversibly decreased the binding of Congo red dye to the PrP amyloid rods while inactivation of prion infectivity was irreversible. In contrast, 1,1,1-trifluoro-2-propanol (TFIP) did not inactivate prion infectivity but like HFIP, TFIP did alter the morphology of the rods and abolished Congo red binding. Solubilization using various solvents and detergents produced monomeric and dimeric PrP that lacked infectivity. Proteinase K resistance of detergent-treated PrP 27-30 showed no correlation with scrapie infectivity. Our results separate prion infectivity from the amyloid properties of PrP 27-30 and underscore the dependence of prion infectivity on PrPsc conformation. These findings also demonstrate that the specific beta-sheet-rich structures required for prion infectivity can be differentiated from those required for amyloid formation.
MH *Amyloid/drug effects/ultrastructure; Animal; Dyes; Hamsters; Human; Male; Prions/chemistry/*pharmacology; Protein Conformation/drug effects; Scrapie/*transmission; Solvents/pharmacology; Support, Non-U.S. Gov't
AD Departments of Neurology, Institute for Neurodegenerative Diseases, San Francisco, California, 94143, USA
SP englisch
PO USA