Since their original identification, prions have represented enigmatic agents that defy the classical concept of genetic inheritance. For almost four decades, the high-resolution structure of PrP^Sc, the infectious and misfolded counterpart of the cellular prion protein (PrP^C), has remained elusive, mostly due to technical challenges posed by its high insolubility and aggregation propensity. As a result, such a lack of information has critically hampered the search for an effective therapy against prion diseases. Nevertheless, multiple attempts to get insights into the structure of PrP^Sc have provided important experimental constraints that, despite being at limited resolution, are paving the way for the application of computer-aided technologies to model the three-dimensional architecture of prions and their templated replication mechanism. Here, we review the most relevant studies carried out so far to elucidate the conformation of infectious PrP^Sc and offer an overview of the most advanced molecular models to explain prion structure and conversion.

自从其最初的鉴定以来，病毒就代表了神秘主义者，它们违背了经典的遗传遗传学概念。近四十年来，PrP ^Sc的高分辨率结构（细胞病毒蛋白（PrP ^C）的传染性和折叠错误的对应物）一直难以捉摸，这主要是由于其高不溶性和聚集倾向带来的技术挑战。结果，这种信息的缺乏严重地阻碍了对针对病毒疾病的有效疗法的寻找。然而，进行了多次尝试以深入了解PrP ^Sc的结构提供了重要的实验约束，尽管分辨率有限，但仍为应用计算机辅助技术建模to病毒的三维体系结构及其模板化复制机制铺平了道路。在这里，我们回顾了迄今为止进行的最相关的研究，以阐明感染性PrP ^Sc的构象，并概述了用于解释病毒结构和转化的最先进的分子模型。