Cooperation of Stop-Transfer and Conservative Sorting Mechanisms in Mitochondrial Protein Transport
Cooperation of Stop-Transfer and Conservative Sorting Mechanisms in Mitochondrial Protein Transport
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DOI：
10.1016/j.cub.2010.05.058
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发表时间：
2010-07-13
期刊：
影响因子：
9.2
通讯作者：
van der Laan, Martin
中科院分区：
文献类型：
--
作者：
Bohnert, Maria;Rehling, Peter;van der Laan, Martin
线粒体内膜是一种高度富含蛋白质的膜，对氧化磷酸化和代谢物转运至关重要[1]。大量的内膜蛋白被合成为具有可裂解前序列的前蛋白[2-9]。前蛋白插入膜的相反机制一直存在争议：内膜中的停止转移与通过基质的保守分选[3，8，10]。我们解剖了多跨膜ABC转运蛋白的膜插入。N-末端膜结构域从内膜的前序列易位酶（TIM 23复合物）通过停止转移机制横向释放，而随后的结构域通过基质热休克蛋白70（mtHsp 70）马达进口并通过氧化酶组装（OXA）易位酶出口。这些观察结果导致了一个意想不到的解决方案，有争议的辩论线粒体前蛋白分选。停止转移和保守分选不是相互排斥的途径，而是代表在具有复杂拓扑结构的蛋白质的膜整合中合作的分选机制。我们的结论是，多跨蛋白插入在一个模块化的方式由两个内膜前蛋白转位酶的协调行动。
The mitochondrial inner membrane is a highly protein-rich membrane with central importance for oxidative phosphorylation and metabolite transport [1]. A large number of inner-membrane proteins are synthesized as preproteins with cleavable presequences [2-9]. Opposing mechanisms of preprotein insertion into the membrane have been debated: stop-transfer with arrest in the inner membrane versus conservative sorting via the matrix [3, 8, 10]. We dissected the membrane insertion of a multispanning ABC transporter. The N-terminal membrane domain was laterally released from the presequence translocase of the inner membrane (TIM23 complex) by a stop-transfer mechanism, whereas the subsequent domain was imported via the matrix heat-shock protein 70 (mtHsp70) motor and exported by the oxidase assembly (OXA) translocase. These observations lead to an unexpected solution to the controversial debate about mitochondrial preprotein sorting. Stop-transfer and conservative sorting are not mutually exclusive pathways but represent sorting mechanisms that cooperate in the membrane integration of a protein with complex topology. We conclude that the multispanning protein is inserted in a modular manner by the coordinated action of two inner-membrane preprotein translocases.