PDF(Pubmed)
Abstract：
To date, there is no general physical model of the mechanism by which unfolded polypeptide chains with different properties are imported into the mitochondria. At the molecular level, it is still unclear how transit polypeptides approach, are captured by the protein translocation machinery in the outer mitochondrial membrane, and how they subsequently cross the entropic barrier of a protein translocation pore to enter the intermembrane space. This deficiency has been due to the lack of detailed structural and dynamic information about the membrane pores. In this review, we focus on the recently determined sub-nanometer cryo-EM structures and our current knowledge of the dynamics of the mitochondrial two-pore outer membrane protein translocation machinery (TOM core complex), which provide a starting point for addressing the above questions. Of particular interest are recent discoveries showing that the TOM core complex can act as a mechanosensor, where the pores close as a result of interaction with membrane-proximal structures. We highlight unusual and new correlations between the structural elements of the TOM complexes and their dynamic behavior in the membrane environment.
摘要：
迄今为止,对于将具有不同性质的未折叠多肽链导入线粒体的机制，没有通用的物理模型。在分子水平上,目前还不清楚转运多肽是如何接近的，被线粒体外膜中的蛋白质易位机制捕获，以及它们随后如何穿过蛋白质易位孔的熵屏障进入膜间隙。这种缺陷是由于缺乏关于膜孔的详细结构和动态信息。在这次审查中,我们专注于最近确定的亚纳米cryo-EM结构和我们目前对线粒体两孔外膜蛋白易位机制（TOM核心复合物）动力学的了解，这为解决上述问题提供了起点。特别令人感兴趣的是最近的发现，表明TOM核心复合体可以充当机械传感器，由于与膜近端结构的相互作用，孔关闭。我们强调了TOM复合物的结构元素与其在膜环境中的动态行为之间的异常和新的相关性。
