Gordon Life Science Institute, 53 South Cottage Road, Belmont, MA 02478, USA.
Curr Top Med Chem. 2013;13(10):1152-63. doi: 10.2174/15680266113139990003.
Transmissible spongiform encephalopathies (TSEs) are prion protein misfolding diseases that involve the accumulation of an abnormal β-sheet-rich prion protein aggregated form (PrP(sc)) of the normal α- helix-rich prion protein (PrP(c)) within the central nervous system (CNS) and other organs. On account of its large size and insolubility properties, characterization of PrP(c) is quite difficult. A soluble intermediate, called PrP(β) or β(o), exhibiting many of the same features as PrP(sc), can be generated using a combination of low pH and/or mild denaturing conditions. Here, we review the current knowledge on the following five issues relevant to the conversion mechanisms of PrP(c) to PrP(sc) : (1) How is the Stability of the Helical Structures in the Native PrP(c) Related to the Primary Structure of the PrP(c) (2) Why the Low pH Solution System is a Ideal Trigger of PrP(c) to PrP(sc) Conversion (3) How are the Structural and Dynamical Characteristics of the α-helixrich Intermediates Determined using NMR Data (4) How are the Premolten (PrP(α4) and PrP(αβ)) and β-Oligomer (PrP(β)) Intermediates Detected and Assayed, and (5) Can the Disordered N-terminal Domain be folded into the Structural Segment? Particularly, Chou's wenxiang diagram (http://en.wikipedia.org/wiki/Wenxiang_diagram) was introduced for providing an intuitive picture. This review may help to further understand the prion protein misfolding mechanism.
传染性海绵状脑病（TSE）是一种朊病毒蛋白错误折叠疾病，涉及中枢神经系统（CNS）和其他器官中正常α-螺旋丰富的朊病毒蛋白（PrP(c)）的异常β-折叠丰富的朊病毒蛋白（PrP(sc)）的积累。由于其体积大且不溶性，PrP(c)的特征描述非常困难。通过使用低 pH 值和/或温和变性条件的组合，可以生成一种可溶性中间产物，称为 PrP(β)或β(o)，其表现出与 PrP(sc)许多相同的特征。在这里，我们回顾了与 PrP(c)转化为 PrP(sc)的转换机制相关的以下五个问题的当前知识：（1）天然 PrP(c)中螺旋结构的稳定性与 PrP(c)的一级结构有何关系（2）为什么低 pH 值溶液系统是 PrP(c)转化为 PrP(sc)的理想触发因素（3）如何使用 NMR 数据确定富含α-螺旋的中间体的结构和动力学特征（4）如何检测和测定预熔解（PrP(α4)和 PrP(αβ))和β-寡聚物（PrP(β)）中间体，以及（5）无规 N 端结构域是否可以折叠到结构片段中？特别是，介绍了 Chou 的温香图（http://en.wikipedia.org/wiki/Wenxiang_diagram）以提供直观的图像。这篇综述可能有助于进一步了解朊病毒蛋白错误折叠机制。
