The most infectious prion protein particles
The most infectious prion protein particles
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DOI：
10.1038/nature03989
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发表时间：
2005-09-08
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：
Silveira, JR;Raymond, GJ;Caughey, B
阿尔茨海默氏症、帕金森氏症和传染性海绵状脑病 (TSE) 等神经退行性疾病的特征是异常蛋白质沉积，通常伴有大的淀粉样原纤维。然而，关于此类原纤维或较小的亚原纤维低聚物是否是疾病的主要原因存在疑问(1,2)。 TSE 中的异常沉积物富含 PrPres，PrP 蛋白的一种蛋白酶抗性形式，能够将正常的蛋白酶敏感形式的蛋白质 (PrPsen) 转化为 PrPres（参考文献 3）。 TSE 可以通过含有 PrPres 的神秘因子（朊病毒）在生物体之间传播（参考文献 4 和 5）。为了系统地评估感染性、转化活性和各种含有 PrPres 的聚集体大小之间的关系，PrPres 被部分分解，按大小分级，并通过光散射和非变性凝胶电泳进行分析。我们的分析表明，就 PrP 含量而言，感染性和转化活性在 17 - 27 nm (300 - 600 kDa) 颗粒中显着达到峰值，而这些活性在大原纤维中明显较低，并且在低聚物中几乎不存在。
Neurodegenerative diseases such as Alzheimer's, Parkinson's and the transmissible spongiform encephalopathies (TSEs) are characterized by abnormal protein deposits, often with large amyloid fibrils. However, questions have arisen as to whether such fibrils or smaller subfibrillar oligomers are the prime causes of disease(1,2). Abnormal deposits in TSEs are rich in PrPres, a protease-resistant form of the PrP protein with the ability to convert the normal, protease-sensitive form of the protein (PrPsen) into PrPres (ref. 3). TSEs can be transmitted between organisms by an enigmatic agent (prion) that contains PrPres (refs 4 and 5). To evaluate systematically the relationship between infectivity, converting activity and the size of various PrPres-containing aggregates, PrPres was partially disaggregated, fractionated by size and analysed by light scattering and non-denaturing gel electrophoresis. Our analyses revealed that with respect to PrP content, infectivity and converting activity peaked markedly in 17 - 27- nm (300 - 600 kDa) particles, whereas these activities were substantially lower in large fibrils and virtually absent in oligomers of