University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Nat Commun. 2020 Apr 9;11(1):1763. doi: 10.1038/s41467-020-15554-9.
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.
能量偶联因子（ECF）转运蛋白负责细菌和古菌中微量营养素的摄取。它们由一个整合膜单元，即 S 组件和一个三部分的 ECF 模块组成。有人提出，当 S 组件与 ECF 模块对接时，它会在膜内翻转，从而介导底物的转运。在这里，我们通过多尺度分子动力学模拟和体外实验来研究叶酸特异性 ECF 转运蛋白的 S 组件的分子倾倒机制。模拟揭示了 ECF 模块周围膜的强烈弯曲，为 S 组件的倾倒提供了驱动力。倾倒状态的稳定性取决于非双层形成脂质的存在，这一点通过叶酸转运活性测量得到了证实。总的来说，我们的数据为叶酸特异性 ECF 转运蛋白提供了一个基于脂质的倾倒机制的证据，该机制可能适用于其他 ECF 转运蛋白。
