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 structures of the core MLA complex, MlaBDEF, from the pathogen A. baumannii, in the apo-, ATP- and ADB-bound states. These structures reveal 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, these data also allows us to propose a molecular mechanism of lipid transport by the MLA system.

中文翻译：

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鲍曼不动杆菌维持脂质不对称性（MLA）内膜复合物的结构和脂质动力学

多耐药细菌是现代医学中的主要威胁。革兰氏阴性球杆菌鲍曼不动杆菌目前在WHO急需新疗法开发的病原体清单上名列前茅。脂质不对称性（MLA）蛋白复合物的维持是在革兰氏阴性细菌中将脂质从外膜转运到外膜的核心机制之一。它还在几种病原体中引起广泛的抗生素耐药性，其中最显着的是鲍曼不动杆菌。然而，其在脂质转运中作用的分子细节仍然很难捉摸。在这里，我们报告了来自致病性鲍曼不动杆菌的核心MLA复合体MlaBDEF的低温电磁结构，处于apo-，ATP-和ADB结合状态。这些结构在复合物的胞质和周质侧揭示了多个脂质结合位点。分子动力学模拟表明它们在膜上的潜在轨迹。与最近报道的大肠杆菌直向同源物的结构一起，这些数据还允许我们提出通过MLA系统进行脂质转运的分子机制。