E. coli outer membrane and interactions with OmpLA.
E. coli outer membrane and interactions with OmpLA.
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DOI：
10.1016/j.bpj.2014.04.024
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发表时间：
2014-06
影响因子：
3.4
通讯作者：
E. Wu;P. Fleming;M. S. Yeom;G. Widmalm;Jeffery B. Klauda;K. Fleming;W. Im
中科院分区：
文献类型：
--
作者：
E. Wu;P. Fleming;M. S. Yeom;G. Widmalm;Jeffery B. Klauda;K. Fleming;W. Im
革兰氏阴性菌的外膜是一种独特的不对称脂质双层，由内小叶中的磷脂（PL）和外小叶中的脂多糖（LPS）组成。它作为选择性屏障的功能对于细菌在许多不同环境中的生存至关重要，并且它还使革兰氏阴性菌比革兰氏阳性菌对抗生素更具抗性。在这里，我们报告的结构特性的模型的大肠杆菌外膜和它的相互作用与外膜磷脂酶A（OmpLA）利用分子动力学模拟。我们的结果表明，给定此处使用的脂质组合物，外膜的疏水厚度比相应的PL双层薄1.3 μ m，这主要是因为较薄的LPS小叶。由于疏水匹配，观察到OmpLA附近的进一步变薄。OmpLA桶的特定形状诱导LPS和PL小叶之间的各种相互作用，导致蛋白质周围的不对称变薄。OmpLA细胞外环和LPS（头基和核心寡糖）之间的相互作用稳定了环构象，动力学降低，导致二级结构变化和环位移相比，在DLPC双层。此外，我们证明，在不对称双层的LPS/PL比可以可靠地估计每种脂质类型的过脂质表面积，并有一个或多或少的LPS在外叶的外膜的整体膜结构没有统计学差异，虽然个别脂质性质略有不同。
The outer membrane of Gram-negative bacteria is a unique asymmetric lipid bilayer composed of phospholipids (PLs) in the inner leaflet and lipopolysaccharides (LPSs) in the outer leaflet. Its function as a selective barrier is crucial for the survival of bacteria in many distinct environments, and it also renders Gram-negative bacteria more resistant to antibiotics than their Gram-positive counterparts. Here, we report the structural properties of a model of theEscherichia coliouter membrane and its interaction with outer membrane phospholipase A (OmpLA) utilizing molecular dynamics simulations. Our results reveal that given the lipid composition used here, the hydrophobic thickness of the outer membrane is ∼3 Å thinner than the corresponding PL bilayer, mainly because of the thinner LPS leaflet. Further thinning in the vicinity of OmpLA is observed due to hydrophobic matching. The particular shape of the OmpLA barrel induces various interactions between LPS and PL leaflets, resulting in asymmetric thinning around the protein. The interaction between OmpLA extracellular loops and LPS (headgroups and core oligosaccharides) stabilizes the loop conformation with reduced dynamics, which leads to secondary structure variation and loop displacement compared to that in a DLPC bilayer. In addition, we demonstrate that the LPS/PL ratios in asymmetric bilayers can be reliably estimated by the per-lipid surface area of each lipid type, and there is no statistical difference in the overall membrane structure for the outer membranes with one more or less LPS in the outer leaflet, although individual lipid properties vary slightly.