Transmissible spongiform encephalopathies are lethal neurodegenerative disorders that present with aggregated forms of the cellular prion protein (PrPC), which are known as PrPSc. Prions from different species vary considerably in their transmissibility to xenogeneic hosts. The variable transmission barriers depend on sequence differences between incoming PrPSc and host PrPC and additionally, on strain-dependent conformational properties of PrPSc. The β2-α2 loop region within PrPC varies substantially between species, with its structure being influenced by the residue types in the 2 amino acid sequence positions 170 (most commonly S or N) and 174 (N or T). In this study, we inoculated prions from 5 different species into transgenic mice expressing either disordered-loop or rigid-loop PrPC variants. Similar β2-α2 loop structures correlated with efficient transmission, whereas dissimilar loops correlated with strong transmission barriers. We then classified literature data on cross-species transmission according to the 170S/N polymorphism. Transmission barriers were generally low between species with the same amino acid residue in position 170 and high between those with different residues. These findings point to a triggering role of the local β2-α2 loop structure for prion transmissibility between different species.
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机译:传染性海绵状脑病是致命的神经退行性疾病,表现为细胞forms病毒蛋白(PrP C sup>)的聚集形式,即PrP Sc sup>。来自不同物种的病毒对异种宿主的传播能力差异很大。可变的传输障碍取决于传入的PrP Sc sup>与宿主PrP C sup>之间的序列差异,另外还取决于PrP Sc sup>的应变依赖性构象特性。 PrP C sup>内的β2-α2环区域在种间存在很大差异,其结构受两个氨基酸序列位置170(最常见的S或N)和174(N或N)的残基类型影响T)。在这项研究中,我们将5种不同物种的病毒接种到了表达无序环或刚性环PrP C sup>变体的转基因小鼠中。相似的β2-α2环结构与有效的传输相关,而相异的环与强大的传输壁垒相关。然后,我们根据170S / N多态性对跨物种传播的文献数据进行分类。在第170位具有相同氨基酸残基的物种之间,传播障碍通常较低,而在具有不同残基的物种之间,传递障碍较高。这些发现表明,局部β2-α2环结构对于不同物种之间的病毒传播具有触发作用。
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