The M-domain controls Hsp104 protein remodeling activity in an Hsp70/Hsp40-dependent manner.
The M-domain controls Hsp104 protein remodeling activity in an Hsp70/Hsp40-dependent manner.
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DOI：
10.1016/j.jmb.2010.07.030
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发表时间：
2010-09-10
影响因子：
5.6
通讯作者：
Tsai FT
中科院分区：
文献类型：
--
作者：
Sielaff B;Tsai FT
酵母Hsp104是一种成环的ATP依赖性蛋白解聚酶，与同源的Hsp70分子伴侣系统一起，具有将应激损伤蛋白从先前聚集状态中拯救出来的显著能力。Hsp70系统的上游和下游功能均已报道，但Hsp70/Hsp40如何与Hsp104蛋白重塑活性偶联仍不清楚。Hsp104是一种多结构域蛋白，具有N-末端结构域、M-结构域和两个串联的AAA+结构域。M-结构域形成85-kDa长的卷曲螺旋，并且是Hsp104分子伴侣家族的标志。虽然Hsp104的三维结构已经确定，但M结构域的功能尚不清楚。在这里，我们证明了M-结构域是必不可少的蛋白质解聚，但对热休克蛋白104 ATP酶和底物转运活动的限制。值得注意的是，将Hsp104 M结构域替换为细菌ClpB的M结构域，反之亦然，切换了物种特异性，使得我们的嵌合体现在与非同源Hsp70/DnaK分子伴侣系统合作。我们的研究结果表明，M结构域控制Hsp104蛋白的重塑活动，在Hsp70/Hsp40依赖的方式，这是释放Hsp104蛋白解聚活性所必需的。
Yeast Hsp104 is a ring-forming, ATP-dependent protein disaggregase that, together with the cognate Hsp70 chaperone system, has the remarkable ability to rescue stress damaged proteins from a previously aggregated state. Both up-stream and down-stream functions for the Hsp70 system have been reported, but it remains unclear how Hsp70/Hsp40 is coupled to the Hsp104 protein remodeling activity. Hsp104 is a multi-domain protein that possesses an N-terminal domain, an M-domain, and two tandem AAA+ domains. The M-domain forms an 85-Å long coiled-coil and is a hallmark of the Hsp104 chaperone family. While the 3D structure of Hsp104 has been determined, the function of the M-domain is unclear. Here, we demonstrate that the M-domain is essential for protein disaggregation but dispensable for the Hsp104 ATPase and substrate translocating activities. Remarkably, replacing the Hsp104 M-domain against that of bacterial ClpB, and vice versa, switches the species-specificity so that our chimeras now cooperate with the non-cognate Hsp70/DnaK chaperone system. Our results demonstrate that the M-domain controls the Hsp104 protein remodeling activities in an Hsp70/Hsp40-dependent manner, which is required to unleash the Hsp104 protein disaggregating activity.
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影响因子：
16
作者：
Tipton, Kimberly A.;Verges, Katherine J.;Weissman, Jonathan S.
通讯作者：
Weissman, Jonathan S.
影响因子：
3
作者：
Boesl, Benjamin;Grimminger, Valerie;Walter, Stefan
通讯作者：
Walter, Stefan
DOI：
10.1073/pnas.1003572107
发表时间：
2010-05-04
影响因子：
11.1
作者：
Lee, Sukyeong;Sielaff, Bernhard;Tsai, Francis T. F.
通讯作者：
Tsai, Francis T. F.
影响因子：
4.8
作者：
Watanabe, Y;Takano, M;Yoshida, M
通讯作者：
Yoshida, M
DOI：
10.1073/pnas.0535717100
发表时间：
2003-03-04
影响因子：
11.1
作者：
Schlothauer, T;Mogk, A;Turgay, K
通讯作者：
Turgay, K