Wang Wenhe, Chen Xudong, Zhang Laixing, Yi Jingbo, Ma Qingxi, Yin Jian, Zhuo Wei, Gu Jinke, Yang Maojun
Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China.
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei China.
Cell Discov. 2020 Sep 29;6:67. doi: 10.1038/s41421-020-00198-2. eCollection 2020.
The translocase of the outer mitochondrial membrane (TOM) complex is the main entry gate for mitochondrial precursor proteins synthesized on cytosolic ribosomes. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the dimeric human TOM core complex (TOM-CC). Two Tom40 β-barrel proteins, connected by two Tom22 receptor subunits and one phospholipid, form the protein-conducting channels. The small Tom proteins Tom5, Tom6, and Tom7 surround the channel and have notable configurations. The distinct electrostatic features of the complex, including the pronounced negative interior and the positive regions at the periphery and center of the dimer on the intermembrane space (IMS) side, provide insight into the preprotein translocation mechanism. Further, two dimeric TOM complexes may associate to form tetramer in the shape of a parallelogram, offering a potential explanation into the unusual structural features of Tom subunits and a new perspective of viewing the import of mitochondrial proteins.
线粒体外膜转位酶（TOM）复合体是胞质核糖体上合成的线粒体前体蛋白的主要入口。本文报道了二聚体人TOM核心复合体（TOM-CC）的单颗粒冷冻电子显微镜（cryo-EM）结构。两个Tom40β桶蛋白由两个Tom22受体亚基和一个磷脂连接，形成蛋白质传导通道。小Tom蛋白Tom5、Tom6和Tom7围绕着通道并具有显著的构象。该复合体独特的静电特征，包括明显的负电内部以及二聚体在膜间隙（IMS）侧的外周和中心的正电区域，为前体蛋白转位机制提供了见解。此外，两个二聚体TOM复合体可能缔合形成平行四边形形状的四聚体，这为Tom亚基不寻常的结构特征提供了一种潜在解释，并为观察线粒体蛋白的导入提供了新的视角。
