Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544.
Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18737-18743. doi: 10.1073/pnas.2007696117. Epub 2020 Jul 16.
The outer membrane (OM) of gram-negative bacteria confers innate resistance to toxins and antibiotics. Integral β-barrel outer membrane proteins (OMPs) function to establish and maintain the selective permeability of the OM. OMPs are assembled into the OM by the β-barrel assembly machine (BAM), which is composed of one OMP-BamA-and four lipoproteins-BamB, C, D, and E. BamB, C, and E can be removed individually with only minor effects on barrier function; however, depletion of either BamA or BamD causes a global defect in OMP assembly and results in cell death. We have identified a gain-of-function mutation, , that bypasses the requirement for BamD. Although ::kan cells exhibit growth and OM barrier defects, they assemble OMPs with surprising robustness. Our results demonstrate that BamD does not play a catalytic role in OMP assembly, but rather functions to regulate the activity of BamA.
革兰氏阴性细菌的外膜（OM）赋予其对毒素和抗生素的先天抗性。整合的β-桶状外膜蛋白（OMP）的功能是建立和维持 OM 的选择性通透性。OMP 由β-桶组装机（BAM）组装到 OM 中，BAM 由一个 OMP-BamA 和四个脂蛋白-BamB、C、D 和 E 组成。BamB、C 和 E 可以单独去除，对屏障功能的影响很小；然而，BamA 或 BamD 的耗尽都会导致 OMP 组装的全局缺陷，并导致细胞死亡。我们已经确定了一种功能获得性突变 ，它可以绕过 BamD 的需求。尽管 ::kan 细胞表现出生长和 OM 屏障缺陷，但它们出人意料地稳健地组装 OMP。我们的结果表明，BamD 在 OMP 组装中不起催化作用，而是起到调节 BamA 活性的作用。
