Su Jiayue, Tian Xuyang, Wang Ziyi, Yang Jiawen, Sun Shan, Sui Sen-Fang
State Key Laboratory of Membrane Biology, Beijing Frontier Research Center for Biological Structure, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
School of Life Sciences, Cryo-EM Center, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China.
PNAS Nexus. 2024 Jul 26;3(7):pgae269. doi: 10.1093/pnasnexus/pgae269. eCollection 2024 Jul.
The translocase of the outer membrane (TOM) complex serves as the main gate for preproteins entering mitochondria and thus plays a pivotal role in sustaining mitochondrial stability. Precursor proteins, featuring amino-terminal targeting signals (presequences) or internal targeting signals, are recognized by the TOM complex receptors Tom20, Tom22, and Tom70, and then translocated into mitochondria through Tom40. By using chemical cross-linking to stabilize Tom20 in the TOM complex, this study unveils the structure of the human TOM holo complex, encompassing the intact Tom20 component, at a resolution of approximately 6 Å by cryo-electron microscopy. Our structure shows the TOM holo complex containing only one Tom20 subunit, which is located right at the center of the complex and stabilized by extensive interactions with Tom22, Tom40, and Tom6. Based on the structure, we proposed a possible translocation mode of TOM complex, by which different receptors could work simultaneously to ensure that the preproteins recognized by them are all efficiently translocated into the mitochondria.
外膜转位酶（TOM）复合体是前体蛋白进入线粒体的主要通道，因此在维持线粒体稳定性方面起着关键作用。具有氨基末端靶向信号（前导序列）或内部靶向信号的前体蛋白被TOM复合体受体Tom20、Tom22和Tom70识别，然后通过Tom40转运到线粒体中。本研究通过化学交联使Tom20在TOM复合体中稳定，利用冷冻电子显微镜以约6 Å的分辨率揭示了包含完整Tom20组分的人TOM全复合体的结构。我们的结构显示TOM全复合体仅包含一个Tom20亚基，该亚基位于复合体的中心位置，并通过与Tom22、Tom40和Tom6的广泛相互作用而稳定。基于该结构，我们提出了TOM复合体一种可能的转运模式，即不同的受体可以同时发挥作用，以确保它们识别的前体蛋白都能有效地转运到线粒体中。
