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

蛋白质跨人类线粒体外膜转运的结构基础（P23）

• 批准号: 495870753
• 金额: --
• 依托单位: Institut für Zellbiochemie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2022
• 资助国家: 德国
• 起止时间: 2021-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/495870753?language=en
• 关键词: Structural; basis; protein; transport; across

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.

绝大多数线粒体蛋白通过TOM复合物输入到细胞器，TOM复合物介导肽通过外膜移位。虽然最近的全息核心TOM复合物的高分辨率结构揭示了这种多亚基孔形成通道的结构，但货物识别，肽易位和移交给下游运输和加工机器的分子机制仍然未知。在这个项目中，我们将使用单粒子冷冻电子显微镜确定与不同货物肽结合的主动转运人TOM复合物的结构。这将为客户肽通过TOM通道的路径和通过线粒体外膜的易位机制提供分子见解。