NR AJIX
AU Peretz,D.; Scott,M.R.D.; Groth,D.; Williamson,R.A.; Burton,D.R.; Cohen,F.E.; Prusiner,S.B.
TI Strain-specified relative conformational stability of the scrapie prion protein
QU Protein Science 2001 Apr; 10(4): 854-63
IA http://www.proteinscience.org/cgi/content/full/10/4/854
PT journal article
AB Studies of prion biology and diseases have elucidated several new concepts, but none was more heretical than the proposal that the biological properties that distinguish different prion strains are enciphered in the disease-causing prion protein (PrPsc). To explore this postulate, we examined the properties of PrPsc from eight prion isolates that propagate in Syrian hamster (SHa). Using resistance to protease digestion as a marker for the undenatured protein, we examined the conformational stabilities of these PrPsc molecules. All eight isolates showed sigmoidal patterns of transition from native to denatured PrPsc as a function of increasing guanidine hydrochloride (GdnHCl) concentration. Half-maximal denaturation occurred at a mean value of 1.48 M GdnHCl for the Sc237, HY, SHa(Me7), and MT-C5 isolates, all of which have approximately 75-d incubation periods; a concentration of 1.08 M was found for the DY strain with a approximately 170-d incubation period and approximately 1.25 M for the SHa(RML) and 139H isolates with approximately 180-d incubation periods. A mean value of 1.39 M GdnHCl for the Me7-H strain with a approximately 320-d incubation period was found. Based on these results, the eight prion strains segregated into four distinct groups. Our results support the unorthodox proposal that distinct PrPsc conformers encipher the biological properties of prion strains.
MH Animal; Antibodies/diagnostic use/genetics; Endopeptidases/diagnostic use; Enzyme-Linked Immunosorbent Assay/methods; Guanidine; Hamsters; Mesocricetus; Prions/*chemistry/*classification; *Protein Conformation; Protein Denaturation/drug effects; Scrapie/*etiology; Species Specificity; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94143, USA
SP englisch
PO USA