Structural basis of protein transport across the outer membrane of human mitochondria (P23)

绝大多数线粒体蛋白是通过TOM复合体进入细胞器的，TOM复合体通过外膜介导肽的转运。尽管最近全息核心TOM复合体的高分辨率结构揭示了这一多亚基成孔通道的结构，但货物识别、多肽转运和移交到下游运输和加工机械的分子机制仍不清楚。在这个项目中，我们将使用单粒子冷冻电子显微镜来确定主动转运与不同货肽结合的人TOM复合体的结构。这将为客户肽通过TOM通道的路径和通过线粒体膜外膜的转位机制提供分子洞察力。

The vast majority of mitochondrial proteins are imported to the organelle through the TOM complex, which mediates peptide translocation through the outer membrane. Although recent high-resolution structures of the holo core TOM complex have shed light on the architecture of this multi-subunit pore-forming channel, the molecular mechanisms of cargo recognition, peptide translocation and handover to downstream transport and processing machineries remain unknown. In this project, we will determine structures of actively transporting human TOM complexes bound to different cargo peptides using single-particle cryo-electron microscopy. This will provide molecular insights into the path of the client peptide through the TOM channel and the mechanisms of translocation through the outer mitochondrial membrane.