Prions are self-propagating infectious protein aggregates of mammals and fungi. The exact mechanism of prion formation is poorly understood. In a recent study, a comparative analysis of the aggregation propensities of chimeric proteins derived from the yeast Sup35p and mouse PrP prion proteins was performed in neuroblastoma cells. The cytosolic expression of the Sup35p domains NM, PrP and fusion proteins thereof revealed that the carboxyterminal domain of PrP (PrP90-230) mediated aggregate formation, while Sup35p N and M domains modulated aggregate size and frequency when fused to the globular domain of PrP. Here we further present co-aggregation studies of chimeric proteins with cytosolic PrP or a huntingtin fragment with an extended polyglutamine tract. Our studies demonstrate that cross-seeding by heterologous proteins requires sequence similarity with the aggregated protein domain. Taken together, these results demonstrate that nucleation and seeding of prion protein aggregates is strongly influenced by dynamic interactions between the aggregate core forming domain and its flanking regions.

中文翻译：

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Sup35p 和 PrP 朊病毒蛋白结构域的动态相互作用调节聚集成核和播种。

朊病毒是哺乳动物和真菌的自我繁殖感染性蛋白质聚集体。对朊病毒形成的确切机制知之甚少。在最近的一项研究中，在神经母细胞瘤细胞中对源自酵母 Sup35p 的嵌合蛋白和小鼠 PrP 朊病毒蛋白的聚集倾向进行了比较分析。Sup35p 结构域 NM、PrP 及其融合蛋白的胞质表达表明，PrP 的羧基末端结构域 (PrP90-230) 介导了聚集体的形成，而 Sup35p N 和 M 结构域在与 PrP 的球状结构域融合时调节了聚集体的大小和频率。在这里，我们进一步介绍了嵌合蛋白与胞质 PrP 或亨廷顿片段与扩展的聚谷氨酰胺束的共聚合研究。我们的研究表明，异源蛋白质的交叉接种需要与聚集的蛋白质结构域的序列相似性。总之，这些结果表明朊病毒蛋白聚集体的成核和播种受到聚集体核心形成域与其侧翼区域之间的动态相互作用的强烈影响。