Membrane mediated toppling mechanism of the folate energy coupling factor transporter

Ignacio Faustino, Haleh Abdizadeh (), Paulo C. T. Souza, Aike Jeucken, Weronika K. Stanek, Albert Guskov, Dirk J. Slotboom and Siewert J. Marrink ()
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Ignacio Faustino: Groningen Biomolecular Sciences and Biotechnology Institute
Haleh Abdizadeh: Groningen Biomolecular Sciences and Biotechnology Institute
Paulo C. T. Souza: Groningen Biomolecular Sciences and Biotechnology Institute
Aike Jeucken: Groningen Biomolecular Sciences and Biotechnology Institute
Weronika K. Stanek: Groningen Biomolecular Sciences and Biotechnology Institute
Albert Guskov: Groningen Biomolecular Sciences and Biotechnology Institute
Dirk J. Slotboom: Groningen Biomolecular Sciences and Biotechnology Institute
Siewert J. Marrink: Groningen Biomolecular Sciences and Biotechnology Institute

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15554-9

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