Pocket delipidation induced by membrane tension or modification leads to a structurally analogous mechanosensitive channel state

Bolin Wang, Benjamin J Lane, Charalampos Kapsalis, James R Ault, Frank Sobott, Hassane El Mkami, Antonio N Calabrese, Antreas C Kalli, Christos Pliotas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.

Original languageEnglish
Pages (from-to)608-622.e5
Number of pages21
JournalStructure
Volume30
Issue number4
Early online date4 Jan 2022
DOIs
Publication statusPublished - 7 Apr 2022

Keywords

  • Lipids
  • MscL
  • MscS
  • Mechnoasensitive channels
  • EPR spectroscopy
  • HDX
  • MD
  • ESSEM
  • Mass spectrometry
  • Force-from-lipid

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