Evaluating prion models based on comprehensive mutation data of mouse PrP.
Evaluating prion models based on comprehensive mutation data of mouse PrP.
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DOI：
10.1016/j.str.2013.12.019
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发表时间：
2014-04
期刊：
影响因子：
5.7
通讯作者：
T. Shirai;M. Saito;A. Kobayashi;M. Asano;M. Hizume;Shino Ikeda;Kenta Teruya;M. Morita;T. Kitamoto
中科院分区：
文献类型：
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作者：
T. Shirai;M. Saito;A. Kobayashi;M. Asano;M. Hizume;Shino Ikeda;Kenta Teruya;M. Morita;T. Kitamoto
尽管有大量证据支持Prion假说，但PrPSc是PrPSc的基本实体，其结构细节仍然难以捉摸。提出了五种互不相容的PrPSc结构主要工作模式。然而，还没有对这些模型进行系统的评估。我们设计了一种系统点突变与基于知识的氨基酸潜能线索相结合的方法。对小鼠PrP蛋白进行了综合诱变实验，检测了各突变体的PrPSc转化效率。基于突变数据，使用线性化方法对模型进行了评估。尽管这些数据与假设核心PrP的N-末端区域转换为β螺旋的模型比其他模型更一致，但也需要进行实质性的修改，以根据最近的实验结果进一步改进当前的模型。
The structural details of the essential entity of prion disease, fibril prion protein (PrPSc), are still elusive despite the large body of evidence supporting the prion hypothesis. Five major working models of PrPScstructure, which are not compatible with each other, have been proposed. However, no systematic evaluation has been performed on those models. We devised a method that combined systematic point mutation with threading on knowledge-based amino acid potentials. A comprehensive mutation experiment was performed on mouse prion protein, and the PrPScconversion efficiency of each mutant was examined. The models were evaluated based on the mutation data by using the threading method. Although the data turned out to be rather more consistent with the models that assumed a conversion of the N-terminal region of core PrP into a β helix than with others, substantial modifications were also required to further improve the current model based on recent experimental results.