Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor
Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor
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DOI：
10.1038/sj.emboj.7601334
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发表时间：
2006-10-04
期刊：
影响因子：
11.4
通讯作者：
Groll, Michael
中科院分区：
文献类型：
--
作者：
Mokranjac, Dejana;Bourenkov, Gleb;Groll, Michael
内膜线粒体转位酶(TIM23)的输入马达通过与mtHsp70结合和释放的循环，介导依赖于ATP的前蛋白转位到线粒体基质中。这一过程的一个基本步骤是通过J辅分子伴侣Tim14刺激mtHsp70的ATPase活性。Tim14与类J蛋白Tim16形成复合体。该复合体的晶体结构表明，这两种蛋白质的保守结构域具有几乎相同的折叠，但完全不同的表面，使它们能够执行不同的功能。Tim14-Tim16二聚体揭示了先前未描述的J和J类结构域的排列。破坏Tim14和Tim16之间的复合体的突变是致命的，这表明复合体的形成是细胞生存的基本要求。我们进一步证明了Tim16对Tim14的辅伴侣活性的严格调控。J结构域与调节蛋白复合体的第一个晶体结构为了解线粒体TIM23转位酶和Hsp70伴侣系统的功能提供了新的见解。
The import motor of the mitochondrial translocase of the inner membrane (TIM23) mediates the ATP-dependent translocation of preproteins into the mitochondrial matrix by cycles of binding to and release from mtHsp70. An essential step of this process is the stimulation of the ATPase activity of mtHsp70 performed by the J cochaperone Tim14. Tim14 forms a complex with the J-like protein Tim16. The crystal structure of this complex shows that the conserved domains of the two proteins have virtually identical folds but completely different surfaces enabling them to perform different functions. The Tim14-Tim16 dimer reveals a previously undescribed arrangement of J and J-like domains. Mutations that destroy the complex between Tim14 and Tim16 are lethal demonstrating that complex formation is an essential requirement for the viability of cells. We further demonstrate tight regulation of the cochaperone activity of Tim14 by Tim16. The first crystal structure of a J domain in complex with a regulatory protein provides new insights into the function of the mitochondrial TIM23 translocase and the Hsp70 chaperone system in general.