Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS
- The University of Chicago, United States
Abstract
Prokaryotic mechanosensitive (MS) channels open by sensing the physical state of the membrane. As such, lipid-protein interactions represent the defining molecular process underlying mechanotransduction. Here, we describe cryo-electron microscopy (cryo-EM) structures of the E. coli small-conductance mechanosensitive channel (MscS) in nanodiscs (ND). They reveal a novel membrane-anchoring fold that plays a significant role in channel activation and establish a new location for the lipid bilayer, shifted ~14 Å from previous consensus placements. Two types of lipid densities are explicitly observed. A phospholipid that 'hooks' the top of each TM2-TM3 hairpin and likely plays a role in force sensing, and a bundle of acyl chains occluding the permeation path above the L105 cuff. These observations reshape our understanding of force-from-lipids gating in MscS and highlight the key role of allosteric interactions between TM segments and phospholipids bound to key dynamic components of the channel.
Data availability
EM maps and atomic models have been deposited at the Electron Microscopy Data Bank (accession numbers EMD-20508, EMD-20510, EMD-20509, and EMD-20148) and the Protein Data Back (entry codes 6PWN, 6PWP and 6PWO).
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MscS Nanodisc with N-terminal His-TagElectron Microscopy Data Bank, EMD-20508.
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MscS NanodiscElectron Microscopy Data Bank, EMD-20510.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (R01GM131191)
- Eduardo Perozo
National Institute of General Medical Sciences (U54GM087519)
- Eduardo Perozo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- José D Faraldo-Gómez, National Heart, Lung and Blood Institute, National Institutes of Health, United States
Version history
- Received: July 24, 2019
- Accepted: December 27, 2019
- Accepted Manuscript published: December 27, 2019 (version 1)
- Version of Record published: January 24, 2020 (version 2)
Copyright
© 2019, Reddy et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS
eLife 8:e50486.
https://doi.org/10.7554/eLife.50486
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