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The pathway and spatial scale for MscS inactivation.

Kishore Kamaraju1, Vladislav Belyy, Ian Rowe

  • 1Department of Biology, University of Maryland, College Park, MD 20742, USA.

The Journal of General Physiology
|June 15, 2011
PubMed
Summary
This summary is machine-generated.

The mechanosensitive channel of small conductance (MscS) inactivates from a closed state, unlike many eukaryotic channels. This inactivation is a separate process from opening, with distinct tension dependencies.

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Cell Physiology

Background:

  • The mechanosensitive channel of small conductance (MscS) acts as a tension-driven osmolyte release valve in bacteria.
  • MscS exhibits opening, adaptation, and inactivation in response to membrane tension.
  • Understanding MscS inactivation is crucial for comprehending cellular mechanotransduction.

Purpose of the Study:

  • To investigate the inactivation transition of Escherichia coli MscS.
  • To determine the tension dependencies and gating states involved in MscS inactivation.
  • To characterize the area change associated with MscS inactivation.

Main Methods:

  • Utilized specialized pressure protocols on excised membrane patches of E. coli.
  • Applied tension steps to stimulate MscS activity and analyzed channel gating.
  • Investigated inactivation in wild-type and mutant MscS channels (A98S, L111S).
  • Estimated area changes (ΔA) associated with inactivation and opening.

Main Results:

  • MscS inactivation is a sequential process distinct from adaptation, with opposite tension dependencies.
  • MscS primarily inactivates from the closed state, not the open state.
  • Mutant analysis suggests independent tension-driven pathways for opening and inactivation.
  • Estimated in-plane expansion (ΔA) for inactivation is 8.5 nm², approximately half that of opening.

Conclusions:

  • MscS inactivation and opening are independent tension-driven processes initiating from the closed state.
  • The lipid-facing TM1-TM2 pairs likely displace during inactivation, uncoupling from the gate.
  • The quantified ΔA provides a constraint for modeling the inactivated state of MscS.