The study of fungal prion proteins affords remarkable opportunities to elucidate both intragenic and extragenic effectors of prion propagation. The yeast prion protein Sup35 and the self-perpetuating [PSI+] prion state is one of the best characterized fungal prions. While there is little sequence homology among known prion proteins, one region of striking similarity exists between Sup35p and the mammalian prion protein PrP. This region is comprised of roughly five octapeptide repeats of similar composition. The expansion of the repeat region in PrP is associated with inherited prion diseases. In order to learn more about the effects of PrP repeat expansions on the structural properties of a protein that undergoes a similar transition to a self-perpetuating aggregate, we generated chimeric Sup35-PrP proteins. Using both in vivo and in vitro systems we described the effect of repeat length on protein misfolding, aggregation, amyloid formation and amyloid stability. We found that repeat expansions in the chimeric prion proteins increase the propensity to initiate prion propagation and enhance the formation of amyloid fibers without significantly altering fiber stability.

中文翻译：

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使用嵌合朊病毒蛋白深入了解朊病毒传播的基因内和基因外效应子。

真菌朊病毒蛋白的研究为阐明朊病毒传播的基因内和基因外效应物提供了绝佳的机会。酵母朊病毒蛋白 Sup35 和自我永存的 [PSI+] 朊病毒状态是表征最好的真菌朊病毒之一。虽然已知朊病毒蛋白之间几乎没有序列同源性，但 Sup35p 和哺乳动物朊病毒蛋白 PrP 之间存在一个惊人相似的区域。该区域由大约五个组成相似的八肽重复组成。PrP 中重复区域的扩展与遗传性朊病毒疾病有关。为了更多地了解 PrP 重复扩展对经历类似转变为自我永存聚合的蛋白质的结构特性的影响，我们生成了嵌合 Sup35-PrP 蛋白质。我们使用体内和体外系统描述了重复长度对蛋白质错误折叠、聚集、淀粉样蛋白形成和淀粉样蛋白稳定性的影响。我们发现嵌合朊病毒蛋白中的重复扩展增加了启动朊病毒传播的倾向并增强了淀粉样纤维的形成，而不会显着改变纤维稳定性。