Abstract
Transporting small molecules across cell membranes is an essential process in cell physiology. Many structurally diverse, secondary active transporters harness transmembrane electrochemical gradients of ions to power the uptake or efflux of nutrients, signalling molecules, drugs and other ions across cell membranes. Transporters reside in lipid bilayers on the interface between two aqueous compartments, where they are energized and regulated by symported, antiported and allosteric ions on both sides of the membrane and the membrane bilayer itself. Here we outline the mechanisms by which transporters couple ion and solute fluxes and discuss how structural and mechanistic variations enable them to meet specific physiological needs and adapt to environmental conditions. We then consider how general bilayer properties and specific lipid binding modulate transporter activity. Together, ion gradients and lipid properties ensure the effective transport, regulation and distribution of small molecules across cell membranes.
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Acknowledgements
D.D. is a Wallenberg Scholar funded by the Knut and Alice Wallenberg Foundation and further acknowledges support from the European Research Council (ERC) Consolidator Grant EXCHANGE (ERC-CoG-820187), The Swedish Research Council (2021-04709) and the Göran Gustafsson Foundation. O.B. is a Howard Hughes Medical Institute (H.H.M.I) Investigator and further acknowledges support from the National Institute of Neurological Disorders and Stroke grant R37NS085318.
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Drew, D., Boudker, O. Ion and lipid orchestration of secondary active transport. Nature 626, 963–974 (2024). https://doi.org/10.1038/s41586-024-07062-3
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DOI: https://doi.org/10.1038/s41586-024-07062-3
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