Structure of bacterial phospholipid transporter MlaFEDB with substrate bound.
Structure of bacterial phospholipid transporter MlaFEDB with substrate bound.
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DOI：
10.7554/elife.62518
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发表时间：
2020-11-25
期刊：
影响因子：
7.7
通讯作者：
Ekiert DC
中科院分区：
文献类型：
--
作者：
Coudray N;Isom GL;MacRae MR;Saiduddin MN;Bhabha G;Ekiert DC
在双膜细菌中，磷脂穿过细胞被膜的运输对于维持外膜屏障至关重要，外膜屏障在毒力和抗生素抗性中起着关键作用。称为Mla的MCE转运系统涉及磷脂运输和外膜完整性，并且包括ABC转运蛋白MlaFEDB。跨膜亚基MlaE与其他转运蛋白的序列相似性最小，整个内膜MlaFEDB复合物的结构仍然未知。在这里，我们报告的cryo-EM结构MlaFEDB在3.05 μ m的分辨率，揭示了遥远的关系，LPS和MacAB转运蛋白，以及真核ABCA/ABCG家庭。一个连续的运输途径从MlaE底物结合位点延伸，通过MlaD的通道，并进入周质。出乎意料的是，两个磷脂结合到MlaFEDB，这表明多个脂质底物可以在每个循环中转运。我们的结构提供了MlaFEDB的底物识别和运输的机制洞察。
In double-membraned bacteria, phospholipid transport across the cell envelope is critical to maintain the outer membrane barrier, which plays a key role in virulence and antibiotic resistance. An MCE transport system called Mla has been implicated in phospholipid trafficking and outer membrane integrity, and includes an ABC transporter, MlaFEDB. The transmembrane subunit, MlaE, has minimal sequence similarity to other transporters, and the structure of the entire inner-membrane MlaFEDB complex remains unknown. Here, we report the cryo-EM structure of MlaFEDB at 3.05 Å resolution, revealing distant relationships to the LPS and MacAB transporters, as well as the eukaryotic ABCA/ABCG families. A continuous transport pathway extends from the MlaE substrate-binding site, through the channel of MlaD, and into the periplasm. Unexpectedly, two phospholipids are bound to MlaFEDB, suggesting that multiple lipid substrates may be transported each cycle. Our structure provides mechanistic insight into substrate recognition and transport by MlaFEDB.