Multistep assembly of the protein import channel of the mitochondrial outer membrane
Multistep assembly of the protein import channel of the mitochondrial outer membrane
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DOI：
10.1038/86253
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发表时间：
2001-04-01
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影响因子：
--
通讯作者：
Ryan, MT
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文献类型：
--
作者：
Model, K;Meisinger, C;Ryan, MT
靶向线粒体的蛋白质通过称为线粒体外膜转位酶 (TOM) 的高分子量复合物转运到细胞器中。该机器的核心是 400 kDa 的多亚基通用输入孔 (GIP)。在这里，我们报告了酵母 GIP 的组装，其中涉及 250 kDa 和 100 kDa 的两个连续中间体。通道衬里 Tom40 的前体首先通过受体蛋白 Tom20 和 Tom22 靶向膜；然后它与 Tom5 组装形成暴露于膜间隙的 250 kDa 中间体。 250 kDa 中间体之后形成与 Tom6 结合的 100 kDa 中间体。通过 Tom7 和 Tom22 的结合，成熟为 400 kDa 复合物。 Tom7 通过促进 400 kDa 复合物的解离以及从 100 kDa 中间体向成熟复合物的转变发挥作用。这些结果表明，400 kDa 复合物和 100 kDa 晚期中间体之间的动态转换允许新的前体亚基整合到预先存在的复合物中。
Proteins targeted to mitochondria are transported into the organelle through a high molecular weight complex called the translocase of the outer mitochondrial membrane (TOM). At the core of this machinery is a multisubunit general import pore (GIP) of 400 kDa. Here we report the assembly of the yeast GIP that involves two successive intermediates of 250 kDa and 100 kDa. The precursor of the channel-lining Tom40 is first targeted to the membrane via the receptor proteins Tom20 and Tom22; it then assembles with Tom5 to form the 250 kDa intermediate exposed to the intermembrane space. The 250 kDa intermediate is followed by the formation of the 100 kDa intermediate that associates with Tom6. Maturation to the 400 kDa complex occurs by association of Tom7 and Tom22. Tom7 functions by promoting both the dissociation of the 400 kDa complex and the transition from the 100 kDa intermediate to the mature complex. These results indicate that the dynamic conversion between the 400 kDa complex and the 100 kDa late intermediate allows integration of new precursor subunits into pre-existing complexes.