Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
Organization for Promotion of Tenure Track, University of Miyazaki, Miyazaki, Japan.
Elife. 2024 Jan 16;12:RP90274. doi: 10.7554/eLife.90274.
Outer membrane proteins (OMPs) are essential components of the outer membrane of Gram-negative bacteria. In terms of protein targeting and assembly, the current dogma holds that a 'β-signal' imprinted in the final β-strand of the OMP engages the β-barrel assembly machinery (BAM) complex to initiate membrane insertion and assembly of the OMP into the outer membrane. Here, we revealed an additional rule that signals equivalent to the β-signal are repeated in other, internal β-strands within bacterial OMPs, by peptidomimetic and mutational analysis. The internal signal is needed to promote the efficiency of the assembly reaction of these OMPs. BamD, an essential subunit of the BAM complex, recognizes the internal signal and the β-signal, arranging several β-strands and partial folding for rapid OMP assembly. The internal signal-BamD ordering system is not essential for bacterial viability but is necessary to retain the integrity of the outer membrane against antibiotics and other environmental insults.
外膜蛋白（OMPs）是革兰氏阴性细菌外膜的重要组成部分。在蛋白质靶向和组装方面，目前的主流观点认为，OMP 最终β-折叠中留下的“β-信号”与β-桶组装机制（BAM）复合物结合，从而启动 OMP 向膜内的插入和组装到外膜中。在这里，我们通过肽模拟和突变分析揭示了另一个规则，即在细菌 OMP 中的其他内部β-折叠中重复了相当于β-信号的信号。内部信号对于促进这些 OMP 组装反应的效率是必需的。BamD 是 BAM 复合物的一个必需亚基，它识别内部信号和β-信号，为快速 OMP 组装排列多个β-折叠和部分折叠。内部信号-BamD 排序系统对于细菌的生存能力不是必需的，但对于保持外膜的完整性以抵抗抗生素和其他环境胁迫是必要的。
