Evidence for a protein mutator in yeast: role of the Hsp70-related chaperone ssb in formation, stability, and toxicity of the [PSI] prion.
Evidence for a protein mutator in yeast: role of the Hsp70-related chaperone ssb in formation, stability, and toxicity of the [PSI] prion.
复制标题
酵母中蛋白质突变子的证据：Hsp70 相关伴侣 ssb 在 [PSI] 朊病毒的形成、稳定性和毒性中的作用。
DOI：
10.1128/mcb.19.12.8103
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发表时间：
1999
影响因子：
5.3
通讯作者：
Zink,AD
中科院分区：
文献类型：
--
作者：
Chernoff,YO;Newnam,GP;Kumar,J;Allen,K;Zink,AD
酵母蛋白为基础的非孟德尔元件[PSI]，朊病毒样形式的释放因子Sup35的繁殖，被证明是由伴侣蛋白Hsp104和Hsp70之间的相互作用调节。虽然Hsp104蛋白的过量生产治愈了[PSI]的细胞，但Hsp70家族的Ssa 1蛋白的过量生产保护了[PSI]免受Hsp104的治愈效果。在这里，我们表明，另一种蛋白质的热休克蛋白70家族，Ssb，以前牵连在新生的多肽折叠和蛋白质周转，表现出影响[PSI]这是相反的Ssa。Ssb过量生产增加，而Ssb消耗减少，[PSI]由过量生产的Hsp104固化。在缺乏Ssb的菌株中，自发的[PSI]形成和由同源或异源Sup35蛋白的过量产生引起的[PSI]诱导都显著增加。这是第一个不相关的细胞蛋白失活促进朊病毒形成的例子。因此Ssb在基于蛋白质的遗传中起作用，这类似于增变基因产物在基于核酸的遗传中所起的作用。Ssb的消耗也降低了过量生产的Sup35的毒性，并导致对[PSI]固化化学试剂盐酸胍的极端敏感性。我们的数据表明，酵母Hsp70家族的各个成员已经偏离彼此在朊病毒繁殖方面的作用，并建议SSB可以作为一个校对组件的酶系统，防止朊病毒聚集体的形成。
Propagation of the yeast protein-based non-Mendelian element [PSI], a prion-like form of the release factor Sup35, was shown to be regulated by the interplay between chaperone proteins Hsp104 and Hsp70. While overproduction of Hsp104 protein cures cells of [PSI], overproduction of the Ssa1 protein of the Hsp70 family protects [PSI] from the curing effect of Hsp104. Here we demonstrate that another protein of the Hsp70 family, Ssb, previously implicated in nascent polypeptide folding and protein turnover, exhibits effects on [PSI] which are opposite those of Ssa. Ssb overproduction increases, while Ssb depletion decreases, [PSI] curing by the overproduced Hsp104. Both spontaneous [PSI] formation and [PSI] induction by overproduction of the homologous or heterologous Sup35 protein are increased significantly in the strain lacking Ssb. This is the first example when inactivation of an unrelated cellular protein facilitates prion formation. Ssb is therefore playing a role in protein-based inheritance, which is analogous to the role played by the products of mutator genes in nucleic acid-based inheritance. Ssb depletion also decreases toxicity of the overproduced Sup35 and causes extreme sensitivity to the [PSI]-curing chemical agent guanidine hydrochloride. Our data demonstrate that various members of the yeast Hsp70 family have diverged from each other in regard to their roles in prion propagation and suggest that Ssb could serve as a proofreading component of the enzymatic system, which prevents formation of prion aggregates.