Structure and lipid dynamics in the A. baumannii maintenance of lipid asymmetry (MLA) inner membrane complex

Structure and lipid dynamics in the A. baumannii maintenance of lipid asymmetry (MLA) inner membrane complex
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鲍曼不动杆菌维持脂质不对称(MLA)内膜复合物的结构和脂质动力学

DOI:
10.1101/2020.05.30.125013
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发表时间:
2020
期刊:
--
影响因子:
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通讯作者:
Mann D
Mann D
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--
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作者:
Mann D

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多重耐药细菌是现代医学的主要威胁。革兰氏阴性球杆菌属鲍曼不动杆菌目前在WHO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。它还有助于在几种病原体中广泛的抗生素耐药性,最突出的是在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仍然在很大程度上habitued. There,我们报告的核心MLA复合物,MlaBDEF,从病原体的冷冻电镜结构。鲍曼不动杆菌,在apo-,ATP-和ADP-结合状态。这些结构揭示了复合物的胞质和周质侧的多个脂质结合位点。分子动力学模拟表明,它们的潜在轨迹穿过膜。与最近报道的大肠杆菌同源物的结构,这些数据也使我们能够提出一个分子机制的脂质运输的MLA系统。
Multi-resistant bacteria are a major threat in modern medicine. The gram-negative coccobacillusAcinetobacter baumanniicurrently 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 inA. 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 pathogenA. 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 theE.coliorthologue, these data also allows us to propose a molecular mechanism of lipid transport by the MLA system.
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