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Membrane mediated toppling mechanism of the folate energy coupling factor transporter

Author

Listed:
  • 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)

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.

Suggested Citation

  • Ignacio Faustino & Haleh Abdizadeh & Paulo C. T. Souza & Aike Jeucken & Weronika K. Stanek & Albert Guskov & Dirk J. Slotboom & Siewert J. Marrink, 2020. "Membrane mediated toppling mechanism of the folate energy coupling factor transporter," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15554-9
    DOI: 10.1038/s41467-020-15554-9
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    Cited by:

    1. Jere P. Segrest & Chongren Tang & Hyun D. Song & Martin K. Jones & W. Sean Davidson & Stephen G. Aller & Jay W. Heinecke, 2022. "ABCA1 is an extracellular phospholipid translocase," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Chancievan Thangaratnarajah & Mark Nijland & Luís Borges-Araújo & Aike Jeucken & Jan Rheinberger & Siewert J. Marrink & Paulo C. T. Souza & Cristina Paulino & Dirk J. Slotboom, 2023. "Expulsion mechanism of the substrate-translocating subunit in ECF transporters," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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