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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Uncoupling of transfer of the presequence and unfolding of the mature domain in precursor translocation across the mitochondrial outer membrane
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Uncoupling of transfer of the presequence and unfolding of the mature domain in precursor translocation across the mitochondrial outer membrane

机译：跨线粒体外膜的前体转运中的先序列转移与成熟结构域的解偶联

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摘要

Translocation of mitochondrial precursor proteins across the mitochondrial outer membrane is facilitated by the translocase of the outer membrane (TOM) complex. By using site-specific photocrosslinking, we have mapped interactious between TOM proteins and a mitochondrial precursor protein arrested at two distinct stages, stage A (accumulated at 0 degree C) and stage B (accumulated at 30 degree C), in the translocation across the outer membrane at high resolution not achieved previously. Allhough the stage A and stage B intermediates were assigned previously to the forms bound to the cis site and the trans site of the TOM complex, respectively, the results of crosslinking indicate that the presequence of the interniediates at both stagc A and stage B is already on the trans side of the outer membrane. The nature domain is unfolded and bound to Tom40 at stage B whereas it remains folded at stage A. After dissociation from the TOM complex, translocation of the stage B intermediate, but not of the stage A intermediate, across the inner membrane was promoted by the intermembrane-space domain of Tom22. We propose a new model for protein lranslocation across the outer membrane, where translocation of the presequence and unfolding of the mature domain are not necessarily coupled.
机译：外膜（TOM）复合物的转位酶促进了线粒体前体蛋白跨线粒体外膜的转运。通过使用位点特异性光交联，我们绘制了TOM蛋白与线粒体前体蛋白之间的相互作用，该蛋白在两个不同的阶段（A阶段（在0摄氏度下累积）和B阶段（在30摄氏度下累积））被捕到，以前无法实现的高分辨率高分辨率外膜。尽管阶段A和阶段B的中间体事先已分别分配给与TOM络合物的顺式位点和反式位点结合的形式，但交联的结果表明，在鹿角A和阶段B的间质的预先序列已经存在。在外膜的反面。自然结构域在B阶段展开并与Tom40结合，而在A阶段保持折叠。从TOM复合体解离后，B阶段中间体（而非A阶段中间体）跨内膜易位。 Tom22的膜间空间域。我们提出了一个新的模型，用于蛋白质在整个外膜中的位置分配，其中先位序列的移位和成熟结构域的展开不一定是耦合的。

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