Riek R, Hornemann S, Wider G, Billeter M, Glockshuber R, Wüthrich K
Institut für Molekularbiologie und Biophysik, Eidgenossische Technische Hochschule-Honggerberg, Zürich, Switzerland.
Nature. 1996 Jul 11;382(6587):180-2. doi: 10.1038/382180a0.
The 'protein only' hypothesis states that a modified form of normal prion protein triggers infectious neurodegenerative diseases, such as bovine spongiform encephalopathy (BSE), or Creutzfeldt-Jakob disease (CJD) in humans. Prion proteins are thought to exist in two different conformations: the 'benign' PrPcform, and the infectious 'scrapie form', PrPsc. Knowledge of the three-dimensional structure of PrPc is essential for understanding the transition to PrPsc. The nuclear magnetic resonance (NMR) structure of the autonomously folding PrP domain comprising residues 121-231 (ref. 6) contains a two-stranded antiparallel beta-sheet and three alpha-helices. This domain contains most of the point-mutation sites that have been linked, in human PrP, to the occurrence of familial prion diseases. The NMR structure shows that these mutations occur within, or directly adjacent to, regular secondary structures. The presence of a beta-sheet in PrP(121-231) is in contrast with model predictions of an all-helical structure of PrPc (ref. 8), and may be important for the initiation of the transition from PrPc to PrPsc.
“仅蛋白质”假说认为，正常朊病毒蛋白的一种修饰形式会引发传染性神经退行性疾病，如牛海绵状脑病（BSE）或人类的克雅氏病（CJD）。朊病毒蛋白被认为以两种不同的构象存在：“良性”的PrPc形式和具有传染性的“瘙痒病形式”PrPsc。了解PrPc的三维结构对于理解向PrPsc的转变至关重要。包含121 - 231位残基的自主折叠PrP结构域的核磁共振（NMR）结构包含一个双股反平行β折叠片和三个α螺旋。该结构域包含了大多数在人类PrP中与家族性朊病毒疾病发生相关的点突变位点。NMR结构表明，这些突变发生在规则二级结构内部或紧邻规则二级结构的位置。PrP(121 - 231)中β折叠片的存在与PrPc全螺旋结构的模型预测相反（参考文献8），并且可能对于启动从PrPc到PrPsc的转变很重要。
