Paschen Stefan A, Waizenegger Thomas, Stan Tincuta, Preuss Marc, Cyrklaff Marek, Hell Kai, Rapaport Doron, Neupert Walter
Adolf-Butenandt-Institut für Physiologische Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5, D-81377 München, Germany.
Nature. 2003 Dec 18;426(6968):862-6. doi: 10.1038/nature02208.
The outer membranes of mitochondria and chloroplasts are distinguished by the presence of beta-barrel membrane proteins. The outer membrane of Gram-negative bacteria also harbours beta-barrel proteins. In mitochondria these proteins fulfil a variety of functions such as transport of small molecules (porin/VDAC), translocation of proteins (Tom40) and regulation of mitochondrial morphology (Mdm10). These proteins are encoded by the nucleus, synthesized in the cytosol, targeted to mitochondria as chaperone-bound species, recognized by the translocase of the outer membrane, and then inserted into the outer membrane where they assemble into functional oligomers. Whereas some knowledge has been accumulated on the pathways of insertion of proteins that span cellular membranes with alpha-helical segments, very little is known about how beta-barrel proteins are integrated into lipid bilayers and assembled into oligomeric structures. Here we describe a protein complex that is essential for the topogenesis of mitochondrial outer membrane beta-barrel proteins (TOB). We present evidence that important elements of the topogenesis of beta-barrel membrane proteins have been conserved during the evolution of mitochondria from endosymbiotic bacterial ancestors.
线粒体和叶绿体的外膜以存在β-桶状膜蛋白为特征。革兰氏阴性菌的外膜也含有β-桶状蛋白。在线粒体中，这些蛋白具有多种功能，如小分子运输（孔蛋白/电压依赖性阴离子通道）、蛋白质转运（外膜转运酶40）和线粒体形态调控（线粒体动力学蛋白10）。这些蛋白由细胞核编码，在细胞质中合成，作为与伴侣蛋白结合的形式靶向线粒体，被外膜转运酶识别，然后插入外膜并组装成功能性寡聚体。虽然对于具有α-螺旋片段的跨细胞膜蛋白的插入途径已经积累了一些知识，但对于β-桶状蛋白如何整合到脂质双层中并组装成寡聚结构却知之甚少。在此，我们描述了一种对于线粒体外膜β-桶状蛋白（TOB）的拓扑形成至关重要的蛋白复合物。我们提供证据表明，β-桶状膜蛋白拓扑形成的重要元件在从内共生细菌祖先进化而来的线粒体过程中得以保留。
