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, Zou W Q
Department of Pathology and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
Cell Mol Life Sci. 2008 Feb;65(4):631-43. doi: 10.1007/s00018-007-7478-z.
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 PrP20, 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 PrP20 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 PrP20 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 PrP20 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.
人类朊病毒疾病的特征是在大脑中积累蛋白酶K（PK）抗性朊病毒蛋白，即PrP27 - 30，可通过针对人类PrP109 - 112的3F4抗体检测到。我们最近在未感染的人类和动物大脑中鉴定出一种新的PK抗性PrP物种，命名为PrP20。尽管在PrP20分子中3F4表位与1E4表位相邻，但它优先被针对人类PrP 97 - 108的1E4抗体检测到，而不是被抗PrP 3F4抗体检测到。本研究表明，去除直至第91位残基的N端氨基酸可显著增加1E4抗体对大脑和培养细胞中PrP的可及性。与表达野生型PrP的细胞相反，表达致病性突变型PrP的细胞不仅积累PrP20，还积累少量3F4检测到的PK抗性PrP27 - 30。值得注意的是，在人类朊病毒疾病过程中，观察到从1E4检测到的PrP20增加到3F4检测到的PrP27 - 30出现的转变。我们的研究表明，PrP*20水平的增加是朊病毒疾病早期阶段的特征。
