DISTINCT PRP PROPERTIES SUGGEST THE MOLECULAR-BASIS OF STRAIN VARIATION IN TRANSMISSIBLE MINK ENCEPHALOPATHY

The molecular basis of strain variation in scrapie diseases is unknown . The only identified component of the agent is the posttranslationall y modified host prion protein (PrPSc). The biochemical and physical pr operties of PrP from two strains of transmissible mink encephalopathy (TME), called hyper (HY) and drowsy (DY), were compared to investigate if PrP heterogeneity could account for Strain diversity. The degradat ion rate of PrPTME digested with proteinase K was found to be strain s pecific and correlated with inactivation of the TME titer. Edman prote in sequencing revealed that the major N-terminal end of HY PrPTME comm enced at least 10 amino acids prior to that of DP PrPTME after digesti on with proteinase K. Analysis of the brain distribution of PrPTME exh ibited a strain-specific pattern and localization of PrPTME to the per ikarya of specific neuron populations. Our findings are consistent wit h HY and DY PrPTME having distinct protein conformations and/or strain -specific ligand interactions that influence PrPTME properties. We pro pose that PrPTME conformation could play a role in targeting TME strai ns to different neuron populations in which strain-specific formation occurs. These data are consistent with the idea that PrPTME protein st ructure determines the molecular basis of strain variation.