Spatial sequestration and oligomer remodeling during de novo [PSI+] formation.
Spatial sequestration and oligomer remodeling during de novo [PSI+] formation.
复制标题
从头 [PSI] 形成过程中的空间隔离和低聚物重塑。
DOI：
10.1080/19336896.2017.1368606
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发表时间：
2017
期刊：
影响因子：
2.3
通讯作者：
Manogaran,AnitaL
中科院分区：
文献类型：
--
作者：
Lyke,DouglasR;Manogaran,AnitaL
朊病毒是一种错误折叠、聚集的感染性蛋白质，存在于从哺乳动物到细菌的一系列生物体中。在哺乳动物中，朊病毒的形成很难研究，因为错误折叠和聚集发生在症状出现之前。对酵母朊病毒 [PSI+]（Sup35p 的错误折叠感染形式）的研究提供了一种实时监测朊病毒形成的易于处理的系统。最近，我们发现朊病毒聚集体的从头形成始于高度移动的细胞质焦点（称为早期焦点）的出现，这些焦点组装成更大的环或点结构。我们还在形成过程中观察到了 SDS 抗性寡聚物，并且含有新形成的寡聚物的裂解物可以将 [psi−] 细胞转化为 [PSI+] 状态，表明这些寡聚物具有感染潜力。在这里，我们进一步表征了朊病毒形成的两个方面：早期病灶的空间隔离和内源性 Sup35p 的寡聚化。我们的数据提供了对朊病毒形成过程的重要见解，并探索了感染性的最低寡聚体要求。
Prions are misfolded, aggregated, infectious proteins found in a range of organisms from mammals to bacteria. In mammals, prion formation is difficult to study because misfolding and aggregation take place prior to symptom presentation. The study of the yeast prion [PSI+], which is the misfolded infectious form of Sup35p, provides a tractable system to monitor prion formation in real time. Recently, we showed that thede novoformation of prion aggregates begins with the appearance of highly mobile cytoplasmic foci, called early foci, which assemble into larger ring or dot structures. We also observed SDS-resistant oligomers during formation, and lysates containing newly formed oligomers can convert [psi−] cells to the [PSI+] state, suggesting that these oligomers have infectious potential. Here, we further characterize two aspects of prion formation: spatial sequestration of early foci and oligomerization of endogenous Sup35p. Our data provides important insights into the process of prion formation and explores the minimal oligomer requirement for infectivity.