1. Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions.
- Author
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Yuan, J., Dong, Z., Guo, J.-P., McGeehan, J., Xiao, X., Wang, J., Cali, I., McGeer, P. L., Cashman, N. R., Bessen, R., Surewicz, W. K., Kneale, G., Petersen, R. B., Gambetti, P., and Zou, W. Q.
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PRION diseases ,EPITOPES ,NEUROBLASTOMA ,CREUTZFELDT-Jakob disease ,PROTEINASES ,AMINO acids - Abstract
Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated PrP27 – 30 detectable by the 3F4 antibody against human PrP109 – 112. We recently identified a new PK-resistant PrP species, designated PrP
*20 , in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97 – 108 but not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP*20 molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic mutant PrP accumulate not only PrP*20 but also a small amount of 3F4-detected PK-resistant PrP27 – 30. Remarkably, during the course of human prion disease, a transition from an increase in 1E4-detected PrP*20 to the occurrence of the 3F4-detected PrP27 – 30 was observed. Our study suggests that an increase in the level of PrP*20 characterizes the early stages of prion diseases. [ABSTRACT FROM AUTHOR]- Published
- 2008
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