Structure and function of protein translocation and localization system

蛋白质在大肠杆菌细胞质膜上的易位是由6个Sec因子组成的Sec机制催化的。其中，SecA分别在ATP结合和水解时经历插入膜和脱插入膜的循环。SecA循环是蛋白质易位的直接驱动力。SecG是机械的一个膜组件，也经历了一个膜拓扑反转循环，该循环与SecA循环耦合。在这个研究项目中，我们发现SecG循环促进SecA循环，从而导致有效的蛋白质易位。此外，还发现了一种加速SecA周期的蛋白质动力。脂蛋白的成熟发生在细胞质膜的外表面。在+2位置有Asp残基以外的脂蛋白从细胞质膜中释放出来并定位到外膜。我们之前发现，LolA是一种脂蛋白特异性分子伴侣，它与外膜定向脂蛋白形成复合物，而不是与具有Asp +2位置的内膜特异性脂蛋白形成复合物。在本研究项目中，我们发现LolB和LolCDE复合物对于脂蛋白的分选和膜特异性定位也是必不可少的。LolB是脂蛋白的外膜受体。LolCDE复合物属于ABC转运超家族，介导脂蛋白从细胞质膜的释放。

Protein translocation across the E.coli cytoplasmic membrane is catalyzed by a Sec macinery comprising six Sec factors. Among them, SecA undergoes the membrane-insertion and -deinsertion cycle upon the binding and hydrolysis of ATP, respectively. The SecA cycle is the direct driving force for protein translocation. SecG, a membrane component of the machinery, also undergoes a membrane topology inversion cycle, which is coupled to the SecA cycle. In this research project, we revealed that the SecG cycle facillitates the SecA cycle, thereby causing efficient protein translocation. Moreover, a protein motive force was also found to accerelate the SecA cycle.Maturation of lipoproteins takes place on the outer surface of the cytoplasmic membrane. Lipoproteins having other than Asp residue at the +2 position are released from the cytoplasmic membrane and localized to the outher membrane. We previously found that LolA, a lipoprotein-specific molecular chaperone in the periplasm, forms a complex with outer membrane-directed lipoprotein, but not inner membrane-specific one having Asp at +2 position. In this research project, we found that LolB and LolCDE complex are also essential for the sorting and membrane-specific localization of lipoproteins. LolB is an outer membrane receptor for lipoprotein. The LolCDE complex belongs to the ABC transport super family and mediates the release of lipoprotein from the cytoplasmic membrane.