Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions

J. Yuan, Z. Dong, J. Guo, John McGeehan, X. Xiao, J. Wang, I. Cali, P. McGeer, N. Cashman, R. Bessen, W. Surewicz, Geoff Kneale, R. Petersen, P. Gambetti, Wen-Quan Zou

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)631-643
Number of pages13
JournalCellular and Molecular Life Sciences (CMLS)
Volume65
Issue number4
DOIs
Publication statusPublished - 2008

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