Molecular basis of polyglutamine disease using yeast

我们观察到亨廷顿蛋白聚集体的结构多态性，亨廷顿蛋白是一种导致亨廷顿病的蛋白质，在体外和体内都是如此。在来自不同脑区的不同构象的亨廷顿蛋白淀粉样蛋白中，纹状体中的那些显示出最高的细胞毒性。因此，淀粉样蛋白构象可能是亨廷顿病区域特异性的关键决定因素。此外，可以检测特定蛋白质和聚谷氨酰胺聚合体之间交叉播种的遗传筛选系统使我们能够识别出一种新的缺少Gln/Asn富含结构域的酵母Pron蛋白。

We observed structural polymorphism in the aggregates of huntingtin, a protein responsible for Huntington disease, both in vitro and in vivo. Among distinct conformations of huntingtin amyloids derived from a variety of brain regions, those in striatum showed the highest cytotoxicity. Therefore, amyloid conformation may be a critical determinant of regional specificity in Huntington disease. In addition, a genetic screening system that can detect cross-seeding between a certain protein and polyglutamine aggregates allows us to identify a novel yeast prion protein that lacks a Gln/Asn-rich domain.