Membrane mediated toppling mechanism of the folate energy coupling factor transporter
Membrane mediated toppling mechanism of the folate energy coupling factor transporter
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DOI：
10.1038/s41467-020-15554-9
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发表时间：
2020-04-09
影响因子：
16.6
通讯作者：
Marrink, Siewert J.
中科院分区：
文献类型：
--
作者：
Faustino, Ignacio;Abdizadeh, Haleh;Marrink, Siewert J.
能量耦合因子（ECF）转运体负责细菌和古细菌对微量营养素的吸收。它们由一个完整的膜单元、s组分和一个三元ECF模块组成。有人提出，当对接到ECF模块时，s组分通过在膜中翻转来介导底物运输。在这里，我们采用多尺度分子动力学模拟和体外实验来研究叶酸特异性ECF转运体s组分的分子倾倒机制。模拟结果显示，ECF模块周围的膜发生了强烈的弯曲，这为s组件的倾覆提供了驱动力。倾覆状态的稳定性取决于非双层形成脂质的存在，正如叶酸运输活性测量所证实的那样。总之，我们的数据为叶酸特异性ECF转运蛋白的脂质依赖性倾覆机制提供了证据，该机制可能适用于其他ECF转运蛋白。能量偶联因子（ECF）转运体负责微量营养素的摄取，并由一个完整的膜单元s组分组成，它赋予底物特异性。本文作者通过多尺度分子动力学模拟和体外实验，研究了叶酸特异性ECF转运体s组分的分子翻转机制。
Energy coupling factor (ECF) transporters are responsible for the uptake of micronutrients in bacteria and archaea. They consist of an integral membrane unit, the S-component, and a tripartite ECF module. It has been proposed that the S-component mediates the substrate transport by toppling over in the membrane when docking onto an ECF module. Here, we present multi-scale molecular dynamics simulations and in vitro experiments to study the molecular toppling mechanism of the S-component of a folate-specific ECF transporter. Simulations reveal a strong bending of the membrane around the ECF module that provides a driving force for toppling of the S-component. The stability of the toppled state depends on the presence of non-bilayer forming lipids, as confirmed by folate transport activity measurements. Together, our data provide evidence for a lipid-dependent toppling-based mechanism for the folate-specific ECF transporter, a mechanism that might apply to other ECF transporters. Energy coupling factor (ECF) transporters are responsible for the uptake of micronutrients and consist of an integral membrane unit, the S-component, which confers substrate specificity. Here, authors present multi-scale molecular dynamics simulations and in vitro experiments to study the molecular toppling mechanism of the S-component of a folate-specific ECF transporter.