Lane, B.J. orcid.org/0000-0002-3563-2716, Ma, Y. orcid.org/0000-0001-5934-0497, Yan, N. orcid.org/0000-0001-8550-2816 et al. (5 more authors) (2024) Monitoring the conformational ensemble and lipid environment of a mechanosensitive channel under cyclodextrin-induced membrane tension. Structure, 32 (6). pp. 739-750. ISSN 0969-2126
Abstract
Membrane forces shift the equilibria of mechanosensitive channels enabling them to convert mechanical cues into electrical signals. Molecular tools to stabilize and methods to capture their highly dynamic states are lacking. Cyclodextrins can mimic tension through the sequestering of lipids from membranes. Here we probe the conformational ensemble of MscS by EPR spectroscopy, the lipid environment with NMR, and function with electrophysiology under cyclodextrin-induced tension. We show the extent of MscS activation depends on the cyclodextrin-to-lipid ratio, and that lipids are depleted slower when MscS is present. This has implications in MscS’ activation kinetics when distinct membrane scaffolds such as nanodiscs or liposomes are used. We find MscS transits from closed to sub-conducting state(s) before it desensitizes, due to the lack of lipid availability in its vicinity required for closure. Our approach allows for monitoring tension-sensitive states in membrane proteins and screening molecules capable of inducing molecular tension in bilayers.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | MscS, EPR, NMR, , electrophysiology, cyclodextrin, mechanosensitive ion channel, PELDOR, DEER, membrane, lipids |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Apr 2024 12:44 |
Last Modified: | 25 Feb 2025 14:54 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.str.2024.02.020 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:211881 |