Pocket delipidation induced by membrane tension or modification leads to a structurally analogous mechanosensitive channel state
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.
Citation
Wang , B , Lane , B J , Kapsalis , C , Ault , J R , Sobott , F , El Mkami , H , Calabrese , A N , Kalli , A C & Pliotas , C 2022 , ' Pocket delipidation induced by membrane tension or modification leads to a structurally analogous mechanosensitive channel state ' , Structure , vol. 30 , no. 4 , pp. 608-622.e5 . https://doi.org/10.1016/j.str.2021.12.004
Publication
Structure
Status
Peer reviewed
ISSN
0969-2126Type
Journal article
Rights
Copyright © 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Description
This project was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) grant (BB/S018069/1) to C.P., who also acknowledges support from the Wellcome Trust (WT) (219999/Z/19/Z) and the Chinese Scholarship Council (CSC) in the form of studentships for B.J.L. and B.W. respectively. A.N.C. is a Sir Henry Dale Fellow jointly funded by the WT and the Royal Society (220628/Z/20/Z). Funding from the BBSRC (BB/M012573/1) enabled the purchase of mass spectrometry equipment.Collections
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