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Variant-specific PSI+ Infection Is Transmitted by Sup35 Polymers within PSI+ Aggregates with Heterogeneous Protein Composition

机译:变异特异性PSI +感染是由具有异质蛋白质组成的PSI +聚集体中的Sup35聚合物传播的

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摘要

The [PSI+] prion is the aggregated self-propagating form of the Sup35 protein from the yeast Saccharomyces cerevisiae. Aggregates of Sup35 in [PSI+] cells exist in different heritable conformations, called “variants,” and they are composed of detergent-resistant Sup35 polymers, which may be closely associated with themselves, other proteins, or both. Here, we report that disassembly of the aggregates into individual Sup35 polymers and non-Sup35 components increases their infectivity while retaining their variant specificity, showing that variant-specific [PSI+] infection can be transmitted by Sup35 polymers alone. Morphological analysis revealed that Sup35 isolated from [PSI+] yeast has the appearance of short barrels, and bundles, which seem to be composed of barrels. We show that the major components of two different variants of [PSI+] are interacting infectious Sup35 polymers and Ssa1/2. Using a candidate approach, we detected Hsp104, Ssb1/2, Sis1, Sse1, Ydj1, and Sla2 among minor components of the aggregates. We demonstrate that Ssa1/2 efficiently binds to the prion domain of Sup35 in [PSI+] cells, but that it interacts poorly with the nonaggregated Sup35 found in [psi] cells. Hsp104, Sis1, and Sse1 interact preferentially with the prion versus nonprion form of Sup35, whereas Sla2 and Ssb1/2 interact with both forms of Sup35 with similar efficiency.
机译:[PSI + ] ion病毒是来自酿酒酵母的Sup35蛋白的聚集的自我繁殖形式。 [PSI + ]细胞中Sup35的聚集体以不同的可遗传构象(称为“变体”)存在,并且由耐去污剂的Sup35聚合物组成,这些聚合物可能与自身,其他蛋白质或都。在这里,我们报告说,将聚集体分解成单独的Sup35聚合物和非Sup35组分会增加其感染性,同时保留其变异体特异性,这表明Sup35聚合物可以传播变异体特异性[PSI + ]感染单独。形态分析表明,从[PSI + ]酵母菌中分离得到的Sup35具有短桶状和束状外观,似乎由桶状组成。我们显示[PSI + ]的两个不同变体的主要成分是相互作用的传染性Sup35聚合物和Ssa1 / 2。使用候选方法,我们在聚集体的次要成分中检测到了Hsp104,Ssb1 / 2,Sis1,Sse1,Ydj1和Sla2。我们证明了Ssa1 / 2有效结合[PSI + ]细胞中Sup35的病毒结构域,但是它与[psi -]中未聚集的Sup35相互作用较弱。细胞。 Hsp104,Sis1和Sse1与Sup35的病毒对非pr病毒形式优先相互作用,而Sla2和Ssb1 / 2与Sup35的两种形式相互作用的效率相似。

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