Cns1 is an activator of the Ssa1 ATPase activity
Cns1 is an activator of the Ssa1 ATPase activity
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DOI：
10.1074/jbc.m402189200
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发表时间：
2004-05-28
影响因子：
4.8
通讯作者：
Buchner, J
中科院分区：
文献类型：
--
作者：
Hainzl, O;Wegele, H;Buchner, J
在越来越多的客户蛋白的折叠过程中，Hsp90是一个关键的介质。分子伴侣与许多伴侣和伴侣蛋白合作来完成其任务。在酿酒酵母中，几种Hsp90的合作伴侣通过一个四肽重复结构域与Hsp90相互作用。在这里，我们发现其中一种蛋白质Cns1与Hsp90和酵母Hsp70蛋白Ssa1结合具有相当的亲和力。这让人想起了Sti1，另一种含有tpr的伴侣蛋白。与Sti1不同，Cns1对Hsp90的atp酶没有影响。然而，它通过加速限速ATP水解步骤，激活Ssa1的ATP酶高达30倍。这种刺激作用是由Cns1的n端含tpr部分介导的，而c端部分则没有作用。竞争实验得出结论，Hsp90和Ssa1竞争结合到Cns1的单个TPR结构域。综上所述，Cns1是Ssa1的有效伴侣。我们的研究结果强调了在Hsp90伴侣周期的背景下，Hsp70功能调控的重要性。
Hsp90 is a key mediator in the folding process of a growing number of client proteins. The molecular chaperone cooperates with many co-chaperones and partner proteins to fulfill its task. In Saccharomyces cerevisiae, several co-chaperones of Hsp90 interact with Hsp90 via a tetratricopeptide repeat (TPR) domain. Here we show that one of these proteins, Cns1, binds both to Hsp90 and to the yeast Hsp70 protein Ssa1 with comparable affinities. This is reminiscent of Sti1, another TPR-containing co-chaperone. Unlike Sti1, Cns1 exhibits no influence on the ATPase of Hsp90. However, it activates the ATPase of Ssa1 up to 30-fold by accelerating the rate-limiting ATP hydrolysis step. This stimulating effect is mediated by the N-terminal TPR-containing part of Cns1, whereas the C-terminal part showed no effect. Competition experiments allow the conclusion that Hsp90 and Ssa1 compete for binding to the single TPR domain of Cns1. Taken together, Cns1 is a potent cochaperone of Ssa1. Our findings highlight the importance of the regulation of Hsp70 function in the context of the Hsp90 chaperone cycle.