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Membrane mediated toppling mechanism of the folate energy coupling factor transporter

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Faustino, Ignacio | Abdizadeh, Haleh | Souza, Paulo, C T | Jeucken, Aike | Stanek, Weronika, K | Guskov, Albert | Slotboom, Dirk, J | Marrink, Siewert, J

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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