Structure and lipid dynamics in the maintenance of lipid asymmetry inner membrane complex of A. baumannii.
Structure and lipid dynamics in the maintenance of lipid asymmetry inner membrane complex of A. baumannii.
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DOI：
10.1038/s42003-021-02318-4
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发表时间：
2021-06-29
影响因子：
5.9
通讯作者：
Bergeron JRC
中科院分区：
文献类型：
--
作者：
Mann D;Fan J;Somboon K;Farrell DP;Muenks A;Tzokov SB;DiMaio F;Khalid S;Miller SI;Bergeron JRC
多重耐药细菌是现代医学的主要威胁。革兰氏阴性球杆菌鲍氏不动杆菌目前在世卫组织急需开发新治疗方法的病原体名单中居首位。脂质不对称蛋白复合物的维持是革兰氏阴性菌将脂质从外膜转运到外膜的核心机制之一。它还导致了几种病原体的广泛抗生素耐药性，最突出的是A。鲍曼不动杆菌。尽管如此，其在脂质转运中的作用的分子细节在很大程度上仍然难以捉摸。在这里，我们报告了来自病原体A的核心MLA复合物MlaBDEF的冷冻电镜图。鲍曼不动杆菌，在载脂蛋白，ATP和ADP结合状态，揭示了多个脂质结合位点的胞质和周质侧的复合物。分子动力学模拟表明，它们的潜在轨迹穿过膜。与最近报道的E.大肠杆菌直系同源物，这些数据也使我们能够提出一个分子机制的脂质转运的MLA系统。丹尼尔Mann等人描述了革兰氏阴性病原体鲍氏不动杆菌中脂质不对称内膜复合物（MlaBDEF）维持的更高分辨率结构。通过这种改进的结构图，作者阐明了MlaE螺旋的二级结构元件，并通过MLA系统报告了潜在的脂质动力学，这可能为未来抗A.鲍曼不动杆菌感染
Multi-resistant bacteria are a major threat in modern medicine. The gram-negative coccobacillus Acinetobacter baumannii currently leads the WHO list of pathogens in critical need for new therapeutic development. The maintenance of lipid asymmetry (MLA) protein complex is one of the core machineries that transport lipids from/to the outer membrane in gram-negative bacteria. It also contributes to broad-range antibiotic resistance in several pathogens, most prominently in A. baumannii. Nonetheless, the molecular details of its role in lipid transport has remained largely elusive. Here, we report the cryo-EM maps of the core MLA complex, MlaBDEF, from the pathogen A. baumannii, in the apo-, ATP- and ADP-bound states, revealing multiple lipid binding sites in the cytosolic and periplasmic side of the complex. Molecular dynamics simulations suggest their potential trajectory across the membrane. Collectively with the recently-reported structures of the E. coli orthologue, this data also allows us to propose a molecular mechanism of lipid transport by the MLA system. Daniel Mann et al. describe a higher-resolution structure of the maintenance of lipid asymmetry inner membrane complex (MlaBDEF) in the Gram-negative pathogen, Acinetobacter baumannii. With this improved structural map, the authors clarify the secondary structure elements of MlaE helices and report on potential lipid dynamics by the MLA system that could inform the development of future therapeutics against A. baumannii infection.
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