Model K, Meisinger C, Prinz T, Wiedemann N, Truscott K N, Pfanner N, Ryan M T
Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg Germany.
Nat Struct Biol. 2001 Apr;8(4):361-70. doi: 10.1038/86253.
Proteins targeted to mitochondria are transported into the organelle through a high molecular weight complex called the translocase of the outer mitochondrial membrane (TOM). At the core of this machinery is a multisubunit general import pore (GIP) of 400 kDa. Here we report the assembly of the yeast GIP that involves two successive intermediates of 250 kDa and 100 kDa. The precursor of the channel-lining Tom40 is first targeted to the membrane via the receptor proteins Tom20 and Tom22; it then assembles with Tom5 to form the 250 kDa intermediate exposed to the intermembrane space. The 250 kDa intermediate is followed by the formation of the 100 kDa intermediate that associates with Tom6. Maturation to the 400 kDa complex occurs by association of Tom7 and Tom22. Tom7 functions by promoting both the dissociation of the 400 kDa complex and the transition from the 100 kDa intermediate to the mature complex. These results indicate that the dynamic conversion between the 400 kDa complex and the 100 kDa late intermediate allows integration of new precursor subunits into pre-existing complexes.
靶向线粒体的蛋白质通过一种称为线粒体外膜转位酶（TOM）的高分子量复合物转运到该细胞器中。该机制的核心是一个400 kDa的多亚基通用导入孔（GIP）。在这里，我们报道了酵母GIP的组装过程，该过程涉及250 kDa和100 kDa的两个连续中间体。通道内衬蛋白Tom40的前体首先通过受体蛋白Tom20和Tom22靶向到膜上；然后它与Tom5组装形成暴露于膜间隙的250 kDa中间体。250 kDa中间体之后形成与Tom6相关联的100 kDa中间体。通过Tom7和Tom22的结合，成熟为400 kDa复合物。Tom7通过促进400 kDa复合物的解离以及从100 kDa中间体向成熟复合物的转变来发挥作用。这些结果表明，400 kDa复合物和100 kDa晚期中间体之间的动态转换允许新的前体亚基整合到预先存在的复合物中。
