Hsp110 chaperones regulate prion formation and propagation in S. cerevisiae by two discrete activities.
Hsp110 chaperones regulate prion formation and propagation in S. cerevisiae by two discrete activities.
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DOI：
10.1371/journal.pone.0001763
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发表时间：
2008-03-12
期刊：
影响因子：
3.7
通讯作者：
Bukau B
中科院分区：
文献类型：
--
作者：
Sadlish H;Rampelt H;Shorter J;Wegrzyn RD;Andréasson C;Lindquist S;Bukau B
酿酒酵母的胞质分子伴侣网络与朊病毒性状的出现和维持密切相关。最近，热休克蛋白110蛋白，Sse1，已被确定为一个核苷酸交换因子（NEF）的细胞溶质热休克蛋白70分子伴侣家族成员，Ssa 1和Ssb1。我们研究了Sse1在[PSI +]（翻译终止因子Sup35的朊病毒形式）从头形成和传播中的作用。正如其他人所观察到的，我们发现Sse 1对于朊病毒的高效传播至关重要。我们的研究结果表明，NEF的活动是必要的，以保持足够的水平的无底物Ssa1。然而，Sse1表现出额外的NEF独立的活动，它刺激体外成核Sup35 NM，朊病毒结构域Sup35。我们还观察到，高水平的Sse 1，而不是无关的NEF，非常有效地抑制热休克蛋白104介导的治愈[PSI +]。两者合计，这些结果表明Sse 1的伴侣样活性，有助于稳定的Sup35朊病毒构象的早期折叠中间体。这种活性对于Sup35过量生产条件下的朊病毒形成不是必需的，然而，它可能与自发的[PSI +]形成以及在Hsp104生理诱导后保护朊病毒性状有关。
The cytosolic chaperone network of Saccharomyces cerevisiae is intimately associated with the emergence and maintenance of prion traits. Recently, the Hsp110 protein, Sse1, has been identified as a nucleotide exchange factor (NEF) for both cytosolic Hsp70 chaperone family members, Ssa1 and Ssb1. We have investigated the role of Sse1 in the de novo formation and propagation of [PSI +], the prion form of the translation termination factor, Sup35. As observed by others, we find that Sse1 is essential for efficient prion propagation. Our results suggest that the NEF activity is required for maintaining sufficient levels of substrate-free Ssa1. However, Sse1 exhibits an additional NEF-independent activity; it stimulates in vitro nucleation of Sup35NM, the prion domain of Sup35. We also observe that high levels of Sse1, but not of an unrelated NEF, very potently inhibit Hsp104-mediated curing of [PSI +]. Taken together, these results suggest a chaperone-like activity of Sse1 that assists in stabilization of early folding intermediates of the Sup35 prion conformation. This activity is not essential for prion formation under conditions of Sup35 overproduction, however, it may be relevant for spontaneous [PSI +] formation as well as for protection of the prion trait upon physiological Hsp104 induction.
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