Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions.
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.
Yuan
J
J
Department of Pathology and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
Dong
Z
Z
Guo
J-P
JP
McGeehan
J
J
Xiao
X
X
Wang
J
J
Cali
I
I
McGeer
P L
PL
Cashman
N R
NR
Bessen
R
R
Surewicz
W K
WK
Kneale
G
G
Petersen
R B
RB
Gambetti
P
P
Zou
W Q
WQ
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
D010446:Peptide Fragments; D011328:Prions