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Ion channels as lipid sensors: from structures to mechanisms

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Abstract

Ion channels play critical roles in cellular function by facilitating the flow of ions across the membrane in response to chemical or mechanical stimuli. Ion channels operate in a lipid bilayer, which can modulate or define their function. Recent technical advancements have led to the solution of numerous ion channel structures solubilized in detergent and/or reconstituted into lipid bilayers, thus providing unprecedented insight into the mechanisms underlying ion channel–lipid interactions. Here, we describe how ion channel structures have evolved to respond to both lipid modulators and lipid activators to control the electrical activities of cells, highlighting diverse mechanisms and common themes.

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Fig. 1: Role of lipids in ion channel function.
Fig. 2: Structural diversity of lipid-gated and other VGL ion channels.
Fig. 3: Mechanisms of lipid action in VGL channels.
Fig. 4: MS channels have evolved diverse structures to respond to membrane tension.
Fig. 5: Mechanisms for sensing membrane tension.
Fig. 6: New insight into MscS function derived from structures solved in lipid membranes.
Fig. 7: Lipid modulation of pLGICs.

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Acknowledgements

This research was funded by grant number 113312 from the Natural Sciences and Engineering Research Council of Canada to J.E.B.

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  1. Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada

    Mackenzie J. Thompson & John E. Baenziger

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Thompson, M.J., Baenziger, J.E. Ion channels as lipid sensors: from structures to mechanisms. Nat Chem Biol 16, 1331–1342 (2020). https://doi.org/10.1038/s41589-020-00693-3

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