Molecular Chaperone Hsp70/Hsp90 Prepares the Mitochondrial Outer Membrane Translocon Receptor Tom71 for Preprotein Loading
Molecular Chaperone Hsp70/Hsp90 Prepares the Mitochondrial Outer Membrane Translocon Receptor Tom71 for Preprotein Loading
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DOI：
10.1074/jbc.m109.023986
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发表时间：
2009-08-28
影响因子：
4.8
通讯作者：
Sha, Bingdong
中科院分区：
文献类型：
--
作者：
Li, Jingzhi;Qian, Xinguo;Sha, Bingdong
靶向线粒体的前蛋白通过外膜复合物的转位酶运输。 Tom70/Tom71 是线粒体前蛋白外膜复合物易位酶的主要表面受体。前蛋白由分子伴侣 Hsp70 和 Hsp90 护送至 Tom70/Tom71。在这里，我们展示了 Tom71 的高分辨率晶体结构以及 Tom71 和 Hsp70/Hsp90 C 末端之间的蛋白质复合物。晶体结构表明 Tom70/Tom71 可能表现出两种不同的状态。在关闭状态下，Tom70/Tom71 的 N 端结构域部分阻断前蛋白结合袋。在开放状态下，N 端结构域移开，前蛋白结合袋完全暴露。 Hsp70/Hsp90 的 C 端 EEVD 基序和 Tom71 之间的复合物形成可以将 Tom71 锁定在开放状态，此时 Tom71 的前蛋白结合袋已准备好接收前蛋白。 Hsp70/Hsp90 和 Tom71 N 端结构域之间的相互作用产生构象变化，可能会增加前蛋白结合袋的体积。 Hsp70/Hsp90 和 Tom71 的复合物形成也在 Tom71 内产生显着的结构域重排，这可能使前蛋白结合口袋更靠近 Hsp70/Hsp90，以促进前蛋白从分子伴侣转移到 Tom71。因此，分子伴侣Hsp70/Hsp90可能起到为前蛋白负载准备线粒体外膜受体Tom71的作用。
The preproteins targeted to the mitochondria are transported through the translocase of the outer membrane complex. Tom70/Tom71 is a major surface receptor of the translocase of the outer membrane complex for mitochondrial preproteins. The preproteins are escorted to Tom70/Tom71 by molecular chaperones Hsp70 and Hsp90. Here we present the high resolution crystal structures of Tom71 and the protein complexes between Tom71 and the Hsp70/Hsp90 C terminus. The crystal structures indicate that Tom70/Tom71 may exhibit two distinct states. In the closed state, the N-terminal domain of Tom70/Tom71 partially blocks the preprotein-binding pocket. In the open state, the N-terminal domain moves away, and the preprotein-binding pocket is fully exposed. The complex formation between the C-terminal EEVD motif of Hsp70/Hsp90 and Tom71 could lock Tom71 in the open state where the preprotein-binding pocket of Tom71 is ready to receive preproteins. The interactions between Hsp70/Hsp90 and Tom71 N-terminal domain generate conformational changes that may increase the volume of the preprotein-binding pocket. The complex formation of Hsp70/Hsp90 and Tom71 also generates significant domain rearrangement within Tom71, which may position the preprotein-binding pocket closer to Hsp70/Hsp90 to facilitate the preprotein transfer from the molecular chaperone to Tom71. Therefore, molecular chaperone Hsp70/Hsp90 may function to prepare the mitochondrial outer membrane receptor Tom71 for preprotein loading.