Energetics of lipid transport by the ABC transporter MsbA is lipid dependent.
Energetics of lipid transport by the ABC transporter MsbA is lipid dependent.
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DOI：
10.1038/s42003-021-02902-8
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发表时间：
2021-12-09
影响因子：
5.9
通讯作者：
van Veen HW
中科院分区：
文献类型：
--
作者：
Guo D;Singh H;Shimoyama A;Guffick C;Tang Y;Rowe SM;Noel T;Spring DR;Fukase K;van Veen HW
ABC多药输出蛋白MsbA介导革兰氏阴性菌中脂多糖和磷脂跨质膜的转运。虽然MsbA的结构特征，脂质运输的能量需求仍然未知。在这里，我们报告说，类似于小分子抗生素和细胞毒性剂的运输，flopping的生理相关的长酰基链1，2-二油酰基（C18）-磷脂酰乙醇胺在蛋白脂质体需要同时输入ATP结合和水解和化学质子梯度作为代谢能量的来源。相比之下，脂多糖的大的六酰化（C12-C14）脂质-A锚的跳动仅是ATP依赖性的。这项研究表明，能量的脂质转运MsbA是脂质依赖性。由于我们的突变分析表明脂质和药物通过MsbA中的中央结合室转运，因此膜中的脂质可用性可以影响药物转运活性，反之亦然。Guo等人对MsbA（革兰氏阴性菌中一种必需的ABC脂质转运蛋白）的底物转运的能量依赖性进行了生化分析。作者研究了MsbA对生理相关脂质的翻转及其对ATP和化学质子梯度的不同依赖性，表明MsbA的脂质转运能量学是脂质依赖性的。
The ABC multidrug exporter MsbA mediates the translocation of lipopolysaccharides and phospholipids across the plasma membrane in Gram-negative bacteria. Although MsbA is structurally well characterised, the energetic requirements of lipid transport remain unknown. Here, we report that, similar to the transport of small-molecule antibiotics and cytotoxic agents, the flopping of physiologically relevant long-acyl-chain 1,2-dioleoyl (C18)-phosphatidylethanolamine in proteoliposomes requires the simultaneous input of ATP binding and hydrolysis and the chemical proton gradient as sources of metabolic energy. In contrast, the flopping of the large hexa-acylated (C12-C14) Lipid-A anchor of lipopolysaccharides is only ATP dependent. This study demonstrates that the energetics of lipid transport by MsbA is lipid dependent. As our mutational analyses indicate lipid and drug transport via the central binding chamber in MsbA, the lipid availability in the membrane can affect the drug transport activity and vice versa. Guo et al. conduct a biochemical analysis of the energy dependence of substrate transport by MsbA, an essential ABC lipid transporter in Gram-negative bacteria. The authors examine the flopping of physiologically relevant lipids by MsbA and their differing dependencies on ATP and chemical proton gradient, demonstrating that the energetics of lipid transport by MsbA is lipid dependent.
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