Wang, B, Lane, BJ, Kapsalis, C et al. (6 more authors) (2022) Pocket delipidation induced by membrane tension or modification leads to a structurally analogous mechanosensitive channel state. Structure. ISSN 0969-2126
Abstract
The mechanosensitive ion channel of large conductance MscL gates in response to membrane tension changes. Lipid removal from transmembrane pockets leads to a concerted structural and functional MscL response, but it remains unknown whether there is a correlation between the tension-mediated state and the state derived by pocket delipidation in the absence of tension. Here, we combined pulsed electron paramagnetic resonance spectroscopy and hydrogen-deuterium exchange mass spectrometry, coupled with molecular dynamics simulations under membrane tension, to investigate the structural changes associated with the distinctively derived states. Whether it is tension- or modification-mediated pocket delipidation, we find that MscL samples a similar expanded subconducting state. This is the final step of the delipidation pathway, but only an intermediate stop on the tension-mediated path, with additional tension triggering further channel opening. Our findings hint at synergistic modes of regulation by lipid molecules in membrane tension-activated mechanosensitive channels.
Metadata
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Keywords: | lipids; MscL; MscS; mechanosensitive channels; EPR spectroscopy; HDX; MD; ESSEM; mass spectrometry; force-from-lipid | ||||||||
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Institution: | The University of Leeds | ||||||||
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Biomolecular Mass Spectroscopy (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
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Depositing User: | Symplectic Publications | ||||||||
Date Deposited: | 17 Dec 2021 13:43 | ||||||||
Last Modified: | 28 Jan 2022 16:06 | ||||||||
Status: | Published online | ||||||||
Publisher: | Elsevier | ||||||||
Identification Number: | https://doi.org/10.1016/j.str.2021.12.004 |