Hsp105α suppresses Hsc70 chaperone activity by inhibiting Hsc70 ATPase activity
Hsp105α suppresses Hsc70 chaperone activity by inhibiting Hsc70 ATPase activity
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DOI：
10.1074/jbc.m407947200
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发表时间：
2004-10-01
影响因子：
4.8
通讯作者：
Hatayama, T
中科院分区：
文献类型：
--
作者：
Yamagishi, N;Ishihara, K;Hatayama, T
HSP105α是HSP105/110家族的哺乳动物成员，是HSP70家族的一个分支亚群。Hsp105α在体内与Hsp70/Hsc70作为复合体结合，在体内外负向调节Hsp70/Hsc70的伴侣活性。在这项研究中，我们研究了Hsp105α调节Hsc70伴侣活性的机制。利用Hsp105α和Hsc70的一系列缺失突变体，我们发现Hsp105α和Hsc70之间的相互作用是Hsp105α抑制Hsc70伴侣活性所必需的。此外，Hsp105α和与Hsc70相互作用的Hsp105α缺失突变体抑制了Hsc70的ATPase活性，并伴随着Hsp105α的ATPase活性的出现。由于Hsp70/Hsc70的ATPase活性对于非天然蛋白质底物的有效折叠是必不可少的，Hsp105α被认为通过抑制Hsp70/Hsc70的ATPase活性来调节Hsp70/Hsc70的底物结合周期，从而发挥Hsp70/Hsc70伴侣系统的负调节作用。
Hsp105alpha is a mammalian member of the HSP105/110 family, a diverged subgroup of the HSP70 family. Hsp105alpha associates with Hsp70/Hsc70 as complexes in vivo and regulates the chaperone activity of Hsp70/Hsc70 negatively in vitro and in vivo. In this study, we examined the mechanisms by which Hsp105alpha regulates Hsc70 chaperone activity. Using a series of deletion mutants of Hsp105alpha and Hsc70, we found that the interaction between Hsp105alpha and Hsc70 was necessary for the suppression of Hsc70 chaperone activity by Hsp105alpha. Furthermore, Hsp105alpha and deletion mutants of Hsp105alpha that interacted with Hsc70 suppressed the ATPase activity of Hsc70, with the concomitant appearance of ATPase activity of Hsp105alpha. As the ATPase activity of Hsp70/Hsc70 is essential for the efficient folding of non-native protein substrates, Hsp105alpha is suggested to regulate the substrate binding cycle of Hsp70/Hsc70 by inhibiting the ATPase activity of Hsp70/Hsc70, thereby functioning as a negative regulator of the Hsp70/Hsc70 chaperone system.