Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.
FEBS J. 2015 Feb;282(3):477-90. doi: 10.1111/febs.13152. Epub 2014 Dec 9.
Amyloids are ordered protein aggregates composed of cross-β sheet structures. Amyloids include prions, defined as infectious proteins, which are responsible for mammalian transmissible spongiform encephalopathies, and fungal prions. Although the conventional view is that typical amyloids are associated with nontransmissible mammalian neurodegenerative diseases such as Alzheimer's disease, increasing evidence suggests that the boundary between transmissible and nontransmissible amyloids is ambiguous. To clarify the mechanism underlying the difference in transmissibility, we investigated the dynamics and the properties of polyglutamine (polyQ) amyloids in yeast cells, in which the polyQ aggregates are not transmissible but can be converted into transmissible amyloids. We found that polyQ had an increased tendency to form aggregates compared to the yeast prion Sup35. In addition, we screened dozens of peptides that converted the nontransmissible polyQ to transmissible aggregates when they flanked the polyQ stretch, and also investigated their cellular dynamics aiming to understand the mechanism of transmission.
淀粉样蛋白是由交叉 β 片层结构组成的有序蛋白聚集体。淀粉样蛋白包括朊病毒，定义为传染性蛋白，它们是哺乳动物传染性海绵状脑病的罪魁祸首，还有真菌朊病毒。尽管传统观点认为典型的淀粉样蛋白与非传染性哺乳动物神经退行性疾病如阿尔茨海默病有关，但越来越多的证据表明，传染性和非传染性淀粉样蛋白之间的界限并不明确。为了阐明传染性差异的机制，我们研究了酵母细胞中聚谷氨酰胺（polyQ）淀粉样蛋白的动力学和特性，其中 polyQ 聚集体不可传播，但可以转化为可传播的淀粉样蛋白。我们发现，与酵母朊病毒 Sup35 相比，polyQ 形成聚集体的趋势增加。此外，我们筛选了数十种肽，当它们侧翼排列在 polyQ 延伸时，这些肽可以将不可传播的 polyQ 转化为可传播的聚集体，我们还研究了它们的细胞动力学，旨在了解传播的机制。
