Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS

  1. Bharat Reddy
  2. Navid Bavi
  3. Allen Lu
  4. Yeonwoo Park
  5. Eduardo Perozo  Is a corresponding author
  1. 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).

The following data sets were generated
    1. Reddy BG
    2. Perozo E
    (2019) MscS Nanodisc
    Electron Microscopy Data Bank, EMD-20510.
    1. Reddy BG
    2. Perozo E
    (2019) MscS DDM
    Electron Microscopy Data Bank, EMD-20509.

Article and author information

Author details

  1. Bharat Reddy

    Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Navid Bavi

    Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Allen Lu

    Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yeonwoo Park

    Department of Ecology and Evolution, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Eduardo Perozo

    Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States
    For correspondence
    eperozo@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7132-2793

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

  1. José D Faraldo-Gómez, National Heart, Lung and Blood Institute, National Institutes of Health, United States

Publication history

  1. Received: July 24, 2019
  2. Accepted: December 27, 2019
  3. Accepted Manuscript published: December 27, 2019 (version 1)
  4. 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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  1. Bharat Reddy
  2. Navid Bavi
  3. Allen Lu
  4. Yeonwoo Park
  5. Eduardo Perozo
(2019)
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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