Cryo-EM Structure of a Bacterial Lipid Transporter YebT
Cryo-EM Structure of a Bacterial Lipid Transporter YebT
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DOI：
10.1016/j.jmb.2019.12.008
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发表时间：
2020-02-14
影响因子：
5.6
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
Liu, Chuan;Ma, Jinying;Zhang, Li
革兰氏阴性菌的外膜（OM）是不对称的，外表面上有脂多糖（LPS），内表面上有磷脂（PL）。OM的这种独特组织使革兰氏阴性菌对许多有毒化学物质具有抗性。如何保持这种不对称分布的脂质已经研究了几十年，以前的报道涉及Mla（OM脂质不对称的维持）系统。此外，革兰氏阴性菌的OM距离合成脂质的内膜（IM）约20 nm。因此，新生脂质如何穿过周质空间到达OM的内表面是另一个有趣的问题。YebT是Mla途径中MlaD的同源物，但其在OM和IM的脂质分布中的作用在很大程度上尚不清楚。在这里，我们报告的第一个高分辨率（类似于3.0埃）冷冻电镜结构的全长E。coliYebT中的底物结合状态。我们的结构与脂质相互作用的细节表明，YebT是一个脂质转运蛋白之间的IM和OM跨越。我们还证明了YebT的对称性不匹配和许多其他构象的YebT揭示了这种脂质通道的内在动力学的存在。并对脂质转运的可能机制进行了简要的讨论。(C)2019爱思唯尔有限公司版权所有。
The outer membrane (OM) of Gram-negative bacteria is asymmetric, with lipopolysaccharides (LPSs) on the outer surface and phospholipids (PLs) on the inner surface. This unique organization of OM makes Gram-negative bacteria resistant to many toxic chemicals. How this asymmetric distribution of lipids is maintained has been studied for decades with previous reports of an Mla (Maintenance of OM Lipid Asymmetry) system to be involved. Furthermore, the OM of Gram-negative bacteria is about 20 nm away from inner membrane (IM) where the lipids are synthesized. Therefore, how nascent lipids travel across the periplasmic space and arrive at the inner surface of OM is another interesting question. YebT is a homologue of MlaD in the Mla pathway, but its role in lipid distribution of the OM and IM is largely unknown. Here we report the first high-resolution (similar to 3.0 angstrom) cryo-EM structure of full-length E. coli YebT in a substrate-bound state. Our structure with details of lipid interaction indicates that YebT is a lipid transporter spanning between IM and OM. We also demonstrate the symmetry mismatch in YebT and the existence of many other conformations of YebT revealing the intrinsic dynamics of this lipid channel. And a brief discussion on possible mechanisms of lipid transport is also included. (C) 2019 Elsevier Ltd. All rights reserved.