title: Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions.
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.
authors.affiliation: Department of Pathology and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yuan
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.forename: J-P
authors.initials: JP
authors.lastname: Guo
authors.forename: J
authors.initials: J
authors.lastname: McGeehan
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: I
authors.initials: I
authors.lastname: Cali
authors.forename: P L
authors.initials: PL
authors.lastname: McGeer
authors.forename: N R
authors.initials: NR
authors.lastname: Cashman
authors.forename: R
authors.initials: R
authors.lastname: Bessen
authors.forename: W K
authors.initials: WK
authors.lastname: Surewicz
authors.forename: G
authors.initials: G
authors.lastname: Kneale
authors.forename: R B
authors.initials: RB
authors.lastname: Petersen
authors.forename: P
authors.initials: P
authors.lastname: Gambetti
authors.forename: W Q
authors.initials: WQ
authors.lastname: Zou
mesh_terms: D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis; D016643:Encephalopathy, Bovine Spongiform / Q000175:diagnosis; D006801:Humans; D009447:Neuroblastoma; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry; D017096:Prion Diseases / Q000175:diagnosis*; D011328:Prions / Q000032:analysis* / Q000737:chemistry* / Q000235:genetics; D014162:Transfection
chemical_list: D010446:Peptide Fragments; D011328:Prions