Molecular architecture of the active mitochondrial protein gate
Molecular architecture of the active mitochondrial protein gate
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DOI：
10.1126/science.aac6428
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发表时间：
2015-09-25
期刊：
影响因子：
56.9
通讯作者：
Endo, Toshiya
中科院分区：
文献类型：
--
作者：
Shiota, Takuya;Imai, Kenichiro;Endo, Toshiya
线粒体在细胞能量学、代谢和信号传导中起着中心作用。外膜转运复合体（TOM复合体）进口大部分线粒体蛋白，但其结构尚不清楚。使用交联方法，我们将活性转运子定位到单个氨基酸残基，揭示了通过Tom40通道的前蛋白的不同转运路径。Tom40的n端片段从细胞质中穿过通道，从膜间空间招募伴侣蛋白，引导疏水前蛋白的转移。该转运体包含三个Tom40 β -桶通道，夹在中心α -螺旋Tom22受体簇和外部调节Tom22蛋白之间。蛋白质易位前三聚体复合物与二聚体异构体交换以组装新的TOM复合物。螺旋受体、桶状通道和伴侣蛋白的动态耦合产生了一种多用途的机制，可以运输大约1000种不同的蛋白质。
Mitochondria fulfill central functions in cellular energetics, metabolism, and signaling. The outer membrane translocator complex (the TOM complex) imports most mitochondrial proteins, but its architecture is unknown. Using a cross-linking approach, we mapped the active translocator down to single amino acid residues, revealing different transport paths for preproteins through the Tom40 channel. An N-terminal segment of Tom40 passes from the cytosol through the channel to recruit chaperones fromthe intermembrane space that guide the transfer of hydrophobic preproteins. The translocator contains three Tom40 beta-barrel channels sandwiched between a central alpha-helical Tom22 receptor cluster and external regulatory Tom proteins. The preprotein-translocating trimeric complex exchanges with a dimeric isoform to assemble new TOM complexes. Dynamic coupling of alpha-helical receptors, beta-barrel channels, and chaperones generates a versatile machinery that transports about 1000 different proteins.