NONGENETIC PROPAGATION OF STRAIN-SPECIFIC PROPERTIES OF SCRAPIE PRION PROTEIN
NONGENETIC PROPAGATION OF STRAIN-SPECIFIC PROPERTIES OF SCRAPIE PRION PROTEIN
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DOI：
10.1038/375698a0
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发表时间：
1995-06-22
期刊：
影响因子：
64.8
通讯作者：
CAUGHEY, B
中科院分区：
文献类型：
--
作者：
BESSEN, RA;KOCISKO, DA;CAUGHEY, B
引起痒病和其他传染性海绵状脑病的感染因子被认为仅由蛋白酶抗性形式的朊蛋白（PrPSc）组成（1-6）。纯蛋白质模型的一个前所未有的要求是，病原体菌株差异的“遗传”必须通过PrPSc结构的稳定变化来介导（2,7,8），而不是通过特定试剂核酸的突变来介导(9)。仓鼠传染性水貂脑病（TME）是一种起源于水貂的痒病样疾病，高（HY）和嗜睡（DY）菌株在PrPSc结构上存在菌株差异（7,8）。虽然HY和DY PrPSc都是由前体朊病毒蛋白（PrPc）翻译后衍生而来，但它们在不同的氨基末端被蛋白酶K切割（参考文献8）。本文研究了PrPSc的这种菌株特异性是否在新的PrPSc形成过程中传递给PrPc。来自HY和DY TME菌株的PrPSc在无细胞系统中将蛋白酶敏感的PrPc转化为两组不同的蛋白酶抗性PrP产物。这些数据提供了具有独特三维结构的PrPSc聚合物自繁殖可能是痒病菌株的分子基础的证据。
THE infectious agents causing scrapie and other transmissible spongiform encephalopathies have been postulated to consist solely of the protease-resistant form of prion protein (PrPSc)(1-6). One unprecedented requirement of the protein-only model is that the 'inheritance' of pathogen strain differences must be mediated by stable variations in PrPSc structure(2,7,8), rather than mutations in an agent-specific nucleic acid(9). Strain differences in PrPSc structure have been described for the hyper (HY) and drowsy (DY) strains of hamster transmissible mink encephalopathy (TME)(7,8), a a scrapie-like disease originating in mink. Although HY and DY PrPSc are both post-translationally derived from the precursor prion protein (PrPc) they are cleaved at different amino-terminal sites by proteinase K (ref. 8). Here we investigate whether this strain-specific property of PrPSc is transmitted to PrPc during formation of new PrPSc. PrPSc from the HY and DY TME strains converted the protease-sensitive PrPc into two distinct sets of protease-resistant PrP products in a cell-free system. These data provide evidence that self-propagation of PrPSc polymers with distinct three-dimensional structures could be the molecular basis of scrapie strains.