Structural snapshot of the mitochondrial protein import gate
Structural snapshot of the mitochondrial protein import gate
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DOI：
10.1111/febs.15661
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发表时间：
2020-12-26
期刊：
影响因子：
5.4
通讯作者：
Endo, Toshiya
中科院分区：
文献类型：
--
作者：
Araiso, Yuhei;Imai, Kenichiro;Endo, Toshiya
线粒体外膜（TOM）复合物的转位酶是大多数线粒体蛋白的主要入口。TOM复合物是由β-桶蛋白Tom 40和六个α-螺旋跨膜（TM）蛋白、受体亚基Tom 20、Tom 22和Tom 70以及调节亚基Tom 5、Tom 6和Tom 7组成的多亚基膜蛋白复合物。虽然自TOM复合物的主要成分被鉴定和表征以来已经过去了近30年，但TOM复合物的结构细节直到最近仍然知之甚少。由于冷冻电子显微镜（EM）技术的快速发展，酵母TOM复合物的高分辨率结构已经变得可用。所鉴定的结构显示含有包括Tom 22在内的五个不同亚基的对称二聚体。基于TOM复合物结构的生化和突变分析揭示了不同类别的易位前体蛋白在Tom 40输入通道内存在不同的易位路径。包括我们的交联分析在内的先前研究表明，完整线粒体中的TOM复合物以含有Tom 22的三聚体复合物的混合物形式存在。此外，缺乏Tom 22的二聚体复合物以及三聚体和二聚体可以处理不同的线粒体前体蛋白集合以跨外膜易位。在这个结构快照中，我们将讨论可能的重排的亚基相互作用后，动态转换的TOM复合物之间的不同亚基组装状态，Tom 22的核心二聚体和三聚体。
The translocase of the outer mitochondrial membrane (TOM) complex is the main entry gate for most mitochondrial proteins. The TOM complex is a multisubunit membrane protein complex consisting of a beta-barrel protein Tom40 and six alpha-helical transmembrane (TM) proteins, receptor subunits Tom20, Tom22, and Tom70, and regulatory subunits Tom5, Tom6, and Tom7. Although nearly 30 years have passed since the main components of the TOM complex were identified and characterized, the structural details of the TOM complex remained poorly understood until recently. Thanks to the rapid development of the cryoelectron microscopy (EM) technology, high-resolution structures of the yeast TOM complex have become available. The identified structures showed a symmetric dimer containing five different subunits including Tom22. Biochemical and mutational analyses based on the TOM complex structure revealed the presence of different translocation paths within the Tom40 import channel for different classes of translocating precursor proteins. Previous studies including our cross-linking analyses indicated that the TOM complex in intact mitochondria is present as a mixture of the trimeric complex containing Tom22. Furthermore, the dimeric complex lacking Tom22, and the trimer and dimer may handle different sets of mitochondrial precursor proteins for translocation across the outer membrane. In this Structural Snapshot, we will discuss possible rearrangement of the subunit interactions upon dynamic conversion of the TOM complex between the different subunit assembly states, the Tom22-containing core dimer and trimer.