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Distinct Forms of Mitochondrial TOM-TIM Supercomplexes Define Signal-Dependent States of Preprotein Sorting

机译:线粒体TOM-TIM超复合物的不同形式定义前蛋白分选的信号依赖状态。

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Mitochondrial import of cleavable preproteins occurs at translocation contact sites, where the translocase of the outer membrane (TOM) associates with the presequence translocase of the inner membrane (TIM23) in a supercomplex. Different views exist on the mechanism of how TIM23 mediates preprotein sorting to either the matrix or inner membrane. On the one hand, two TIM23 forms were proposed, a matrix transport form containing the presequence translocase-associated motor (PAM; TIM23-PAM) and a sorting form containing Tim21 (TIM23SORT). On the other hand, it was reported that TIM23 and PAM are permanently associated in a single-entity translocase. We have accumulated distinct transport intermediates of preproteins to analyze the translocases in their active, preprotein-carrying state. We identified two different forms of active TOM-TIM23 supercomplexes, TOM-TIM23SORT and TOM-TIM23-PAM. These two supercomplexes do not represent separate pathways but are in dynamic exchange during preprotein translocation and sorting. Depending on the signals of the preproteins, switches between the different forms of supercomplex and TIM23 are required for the completion of preprotein import.
机译:线粒体可裂解前蛋白的导入发生在易位接触位点,在这种情况下,外膜(TOM)的转位酶与内膜(TIM23)的先序列转位酶缔合。关于TIM23如何介导前蛋白分选到基质或内膜的机制,存在不同的观点。一方面,提出了两种TIM23形式,一种是包含与序列前转位酶相关的马达(PAM; TIM23-PAM)的矩阵运输形式,另一种是包含Tim21的排序形式(TIM23 SORT )。另一方面,据报道TIM23和PAM在单实体转位酶中永久相关。我们已经积累了不同的前蛋白运输中间体,以分析处于活性,前蛋白携带状态的转位酶。我们确定了两种不同形式的活性TOM-TIM23超复合物,即TOM-TIM23 SORT 和TOM-TIM23-PAM。这两个超级复合体并不代表单独的途径,而是在蛋白前转运和分选过程中动态交换。根据前蛋白的信号,需要完成不同形式的超复合物和TIM23之间的切换才能完成前蛋白的导入。

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