外膜转位酶
线粒体内膜
线粒体载体
内膜转移酶
细胞生物学
线粒体膜转运蛋白
胞浆
蛋白质靶向
内膜
生物
线粒体
化学
生物化学
膜蛋白
细菌外膜
膜
酶
大肠杆菌
基因
作者
Xueyin Zhou,Yunxu Yang,Guopeng Wang,Shanshan Wang,Dongjie Sun,Xiaomin Ou,Yuke Lian,Long Li
标识
DOI:10.1101/2023.06.21.546012
摘要
Abstract Most mitochondrial proteins need to be imported from the cytosol. Over half of mitochondrial proteins are imported through the pre-sequence pathway that is controlled by the TOM complex in the outer membrane and the TIM23 complex in the inner membrane. It is unclear on the molecular level how proteins cross the mitochondrial double membranes through the TOM and TIM23 complexes. Here, we report the assembly of the active TOM-TIM23 supercomplex with translocating polypeptide substrates captured in the import pathway. Electron cryo-microscopy (Cryo-EM) analyses reveal that during translocation across the outer membrane, the polypeptide substrates pass through the center of the Tom40 channel while interacting with a glutamine-rich patch in the inner wall of Tom40. Structural and biochemical analyses show that the TIM23 complex contains a heterotrimer of the subunits Tim23, Tim17, and Mgr2 in the inner membrane. Tim17 and Mgr2 shield the polypeptide substrates from the lipid environment. The import pathway consists of two highly conserved residue patches of Tim17, one negatively charged patch at the entrance and one hydrophobic patch in the middle of the pathway. These data reveal an unexpected pre-sequence pathway mediated by the TOM-TIM23 supercomplex for facilitating protein import across the double membranes of mitochondria.
科研通智能强力驱动
Strongly Powered by AbleSci AI