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 (TOM) 复合物的转位酶是胞质核糖体上合成的线粒体前体蛋白的主要入口。在这里，我们报告了二聚体人 TOM 核心复合物 (TOM-CC) 的单颗粒冷冻电子显微镜 (cryo-EM) 结构。两个 Tom40 β-桶蛋白通过两个 Tom22 受体亚基和一种磷脂连接，形成蛋白质传导通道。小 Tom 蛋白 Tom5、Tom6 和 Tom7 围绕通道并具有显着的结构。该复合物的独特静电特征，包括明显的负内部以及膜间空间 (IMS) 侧二聚体外围和中心的正区域，提供了对前蛋白易位机制的深入了解。此外，两个二聚体TOM复合物可能结合形成平行四边形的四聚体，这为Tom亚基的不寻常结构特征提供了潜在的解释，并为观察线粒体蛋白的导入提供了新的视角。