Prions of lower eukaryotes are self-templating protein aggregates that replicate by converting homotypic proteins into stable, tightly packed beta-sheet-rich protein assemblies. Propagation is mediated by prion domains, low-complexity regions enriched in polar and devoid of charged amino acid residues. In mammals, compositionally similar domains modulate the assembly of dynamic stress granules (SGs) that associate via multivalent weak interactions. Dysregulation of SGs composed of proteins with prion-like domains has been proposed to underlie the formation of pathological inclusions in several neurodegenerative diseases. The events that drive prion-like domains into transient or solid assemblies are not well understood. We studied the interactors of the prototype prion domain NM of Saccharomyces cerevisiae Sup35 in its soluble or fibril-induced prion conformation in the mammalian cytosol. We show that the interactomes of soluble and prionized NM overlap with that of SGs. Prion induction by exogenous seeds does not cause SG assembly, demonstrating that colocalization of aberrant protein inclusions with SG components does not necessarily reveal SGs as initial sites of protein misfolding.

中文翻译：

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原纤维诱导的富含谷氨酰胺/天冬酰胺的病毒在哺乳动物细胞中募集应激颗粒蛋白。

低等真核生物的病毒是自我模板化的蛋白质聚集体，可通过将同型蛋白质转化为稳定，紧密堆积的富含β-折叠的蛋白质组装体进行复制。传播是由ion蛋白域，富含极性的低复杂性区域和缺乏带电荷的氨基酸残基介导的。在哺乳动物中，组成相似的域调节通过多价弱相互作用缔合的动态应力颗粒（SG）的组装。已经提出由具有with病毒样结构域的蛋白质组成的SGs的失调是一些神经退行性疾病中病理包涵体形成的基础。将病毒样结构域驱动到瞬态或实体装配中的事件尚不清楚。我们研究了酿酒酵母病毒原型蛋白NM的相互作用因子。Sup35在哺乳动物细胞溶胶中呈可溶性或原纤维诱导的病毒构象。我们显示可溶性和重金属化NM与SGs的相互作用。外源种子对病毒的诱导不会引起SG组装，这表明异常蛋白质包裹体与SG组分的共定位并不一定表明SGs是蛋白质错误折叠的起始位点。