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Insights into the bilayer-mediated toppling mechanism of a folate-specific ECF transporter by cryo-EM.

Thangaratnarajah C, Rheinberger J, Paulino C, Slotboom DJ
Proc Natl Acad Sci U S A 118 (2021)
Cited: 6 times
EuropePMC logo PMID: 34408021

Abstract

Energy-coupling factor (ECF)-type transporters are small, asymmetric membrane protein complexes (∼115 kDa) that consist of a membrane-embedded, substrate-binding protein (S component) and a tripartite ATP-hydrolyzing module (ECF module). They import micronutrients into bacterial cells and have been proposed to use a highly unusual transport mechanism, in which the substrate is dragged across the membrane by a toppling motion of the S component. However, it remains unclear how the lipid bilayer could accommodate such a movement. Here, we used cryogenic electron microscopy at 200 kV to determine structures of a folate-specific ECF transporter in lipid nanodiscs and detergent micelles at 2.7- and 3.4-Å resolution, respectively. The structures reveal an irregularly shaped bilayer environment around the membrane-embedded complex and suggest that toppling of the S component is facilitated by protein-induced membrane deformations. In this way, structural remodeling of the lipid bilayer environment is exploited to guide the transport process.

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  1. Comprehensive Collection and Prediction of ABC Transmembrane Protein Structures in the AI Era of Structural Biology. Tordai H, Suhajda E, Sillitoe I, Nair S, Varadi M, Hegedus T. Int J Mol Sci 23 8877 (2022)


Articles citing this publication (5)

  1. Distinct Energy-Coupling Factor Transporter Subunits Enable Flavin Acquisition and Extracytosolic Trafficking for Extracellular Electron Transfer in Listeria monocytogenes. Rivera-Lugo R, Huang S, Lee F, Méheust R, Iavarone AT, Sidebottom AM, Oldfield E, Portnoy DA, Light SH. mBio 14 e0308522 (2023)
  2. Expulsion mechanism of the substrate-translocating subunit in ECF transporters. Thangaratnarajah C, Nijland M, Borges-Araújo L, Jeucken A, Rheinberger J, Marrink SJ, Souza PCT, Paulino C, Slotboom DJ. Nat Commun 14 4484 (2023)
  3. Bidirectional ATP-driven transport of cobalamin by the mycobacterial ABC transporter BacA. Nijland M, Lefebvre SN, Thangaratnarajah C, Slotboom DJ. Nat Commun 15 2626 (2024)
  4. Identification of inhibitors targeting the energy-coupling factor (ECF) transporters. Diamanti E, Souza PCT, Setyawati I, Bousis S, Monjas L, Swier LJYM, Shams A, Tsarenko A, Stanek WK, Jäger M, Marrink SJ, Slotboom DJ, Hirsch AKH. Commun Biol 6 1182 (2023)
  5. The S-component fold: a link between bacterial transporters and receptors. Partipilo M, Jan Slotboom D. Commun Biol 7 610 (2024)


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