True Heather L, Kalastavadi Tejas, Tank Elizabeth M H
Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Prion. 2008 Apr-Jun;2(2):45-7. doi: 10.4161/pri.2.2.6509. Epub 2008 Apr 17.
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.
对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因子提供了显著的机会。酵母朊病毒蛋白Sup35和自我延续的[PSI+]朊病毒状态是特征最明确的真菌朊病毒之一。虽然已知的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之间存在一个显著相似的区域。该区域由大约五个组成相似的八肽重复序列组成。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重复序列扩展对经历类似转变为自我延续聚集体的蛋白质结构特性的影响，我们构建了嵌合Sup35-PrP蛋白。利用体内和体外系统，我们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序列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，而不会显著改变纤维稳定性。
