Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions |
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| Authors: | J Yuan Z Dong J-P Guo J McGeehan X Xiao J Wang I Cali P L McGeer N R Cashman R Bessen W K Surewicz G Kneale R B Petersen P Gambetti W Q Zou |
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| Institution: | (1) Department of Pathology and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA;(2) Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada;(3) Biophysics Laboratories, Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth, PO1 2DT, United Kingdom;(4) Brain Research Centre, University of British Columbia Hospital, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada;(5) Department of Veterinary Molecular Biology, Montana State University, P.O. Box 173610, Bozeman, Montana 59717, USA;(6) Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA;(7) Department of Neuroscience, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA |
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| 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.
Received 17 October 2007; received after revision 5 December 2007; accepted 14 December 2007 |
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| Keywords: | Prion protein prion disease epitope gene 5 protein neuroblastoma cell Creutzfeldt-Jakob disease |
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