Specificity of the J-protein Sis1 in the propagation of 3 yeast prions
Specificity of the J-protein Sis1 in the propagation of 3 yeast prions
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DOI：
10.1073/pnas.0808934105
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发表时间：
2008-10-28
影响因子：
11.1
通讯作者：
Craig, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Higurashi, Takashi;Hines, Justin K.;Craig, Elizabeth A.
[PSI+]、[PNQ(+)]和[URE3]等酵母蛋白蛋白是由能够获得自持构象的蛋白质形成的可遗传元件。它们的繁殖依赖于淀粉样蛋白复合体的碎裂，淀粉样蛋白复合体形成的淀粉样蛋白复合体产生额外的种子，这些种子是将新生的可溶性蛋白转化为普里恩构象所必需的。我们报道，除了已知的在[RNQ(+)]繁殖中的作用外，Sis1是Hsp70 SSA的J蛋白辅伴侣，也是[PSI+]和[URE3]繁殖所特需的。而[RNQ(+)]和[URE3]在SIS1抑制后都能迅速治愈，[PSI+]丢失明显较慢。这种差异不能简单地用种子数量的差异来解释，因为当抑制Hsp104时，[RNQ(+)]和[PSI+]以相似的动力学丢失，Hsp104是一种重塑蛋白，是所有酵母蛋白繁殖所必需的。相反，在[PSI+]的情况下，我们的结果与Sis1耗尽时PrP复合体的部分损伤，而不是完全消除是一致的。我们认为，一组共同的分子伴侣，J-蛋白SIS1，Hsp70 SSA，和AAA+ATPase Hsp104，在所有酵母Pron的碎裂中依次起作用，但每个Prion所需的Sis1活性阈值是不同的。
Yeast prions, such as [PSI+], [PNQ(+)], and [URE3], are heritable elements formed by proteins capable of acquiring self-perpetuating conformations. Their propagation is dependent on fragmentation of the amyloid protein complexes formed to generate the additional seeds necessary for conversion of nascent soluble protein to the prion conformation. We report that, in addition to its known role in [RNQ(+)] propagation, Sis1, a J-protein cochaperone of Hsp70 Ssa, is also specifically required for propagation of [PSI+] and [URE3]. Whereas both [RNQ(+)] and [URE3] are cured rapidly upon SIS1 repression, [PSI+] loss is markedly slower. This disparity cannot be explained simply by differences in seed number, as [RNQ(+)] and [PSI+] are lost with similar kinetics upon inhibition of Hsp104, a remodeling protein required for propagation of all yeast prions. Rather, in the case of [PSI+], our results are consistent with the partial impairment, rather than the complete abolition, of fragmentation of prion complexes upon Sis1 depletion. We suggest that a common set of molecular chaperones, the J-protein Sis1, the Hsp70 Ssa, and the AAA+ ATPase Hsp104, act sequentially in the fragmentation of all yeast prions, but that the threshold of Sis1 activity required for each prion varies.