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Multifunctional, Micropipette-based Method for Incorporation And Stimulation of Bacterial Mechanosensitive Ion Channels in Droplet Interface Bilayers
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A structural mechanism for MscS gating in lipid bilayers.

Valeria Vásquez1, Marcos Sotomayor, Julio Cordero-Morales

  • 1Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.

Science (New York, N.Y.)
|August 30, 2008
PubMed
Summary

Mechanosensitive channel of small conductance (MscS) structural changes were revealed during osmotic stress response. Helix tilting and expansion in MscS activate the channel pore for water passage.

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Area of Science:

  • Membrane biophysics
  • Prokaryotic cell biology
  • Ion channel function

Background:

  • Mechanosensitive channels of small conductance (MscS) are crucial for prokaryotic survival under osmotic stress.
  • Understanding MscS gating mechanisms is vital for cellular homeostasis.

Purpose of the Study:

  • To elucidate the structural rearrangements of MscS during activation in lipid bilayers.
  • To correlate structural dynamics with channel function.

Main Methods:

  • Functional measurements and electron paramagnetic resonance (EPR) spectroscopy.
  • Computational modeling and analysis.
  • Asymmetric incorporation of lysophospholipids to trap open states.

Main Results:

  • MscS activation involves downward tilting of the TM1-TM2 hairpin.
  • TM3 helices expand, tilt, and rotate, widening the permeation pathway.
  • Increased water accessibility around TM3 was observed in the open state.

Conclusions:

  • The determined open MscS structure aligns with conductance measurements.
  • Helix tilting is a key mechanism for pore widening in mechanosensitive channels.