NMR structure of the mouse prion protein domain PrP(121-231)
NMR structure of the mouse prion protein domain PrP(121-231)
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DOI：
10.1038/382180a0
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发表时间：
1996-07-11
期刊：
影响因子：
64.8
通讯作者：
Wuthrich, K
中科院分区：
文献类型：
--
作者：
Riek, R;Hornemann, S;Wuthrich, K
“仅蛋白质”假说（1）指出，正常朊病毒蛋白的修饰形式引发传染性神经退行性疾病，如牛海绵状脑病（BSE）或人类克雅氏病（CJD）（2-4）。朊病毒蛋白被认为以两种不同的构象存在：“良性”PrPC形式和感染性“瘙痒症形式”PrPSc。了解PrPC的三维结构对于理解向PrPSc的过渡至关重要。包含残基121-231的自主折叠PrP结构域的核磁共振（NMR）结构（参考文献6）包含一个双链反平行β折叠和三个α螺旋。该结构域包含大多数与人类PrP家族性朊病毒疾病发生相关的点突变位点（7）。NMR结构表明，这些突变发生在规则二级结构内或直接邻近规则二级结构。PrP中β折叠的存在（121-231）与PrPC全螺旋结构的模型预测（参考文献8）相反，可能对PrPC向PrPSc转变的起始很重要。
THE 'protein only' hypothesis(1) 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(2-4). Prion proteins are thought to exist in two different conformations(5): the 'benign' PrPC form, and the infections '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(7). 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.