The mechanosensitive channel of small conductance (MscS) functions as a Jack-in-the box

Hannah R. Malcolm, Paul Blount, Joshua A. Maurer

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Phenotypical analysis of the lipid interacting residues in the closed state of the mechanosensitive channel of small conductance (MscS) from Escherichia coli (E. coli) has previously shown that these residues are critical for channel function. In the closed state, mutation of individual hydrophobic lipid lining residues to alanine, thus reducing the hydrophobicity, resulted in phenotypic changes that were observable using in vivo assays. Here, in an analogous set of experiments, we identify eleven residues in the first transmembrane domain of the open state of MscS that interact with the lipid bilayer. Each of these residues was mutated to alanine and leucine to modulate their hydrophobic interaction with the lipid tail-groups in the open state. The effects of these changes on channel function were analyzed using in vivo bacterial assays and patch clamp electrophysiology. Mutant channels were found to be functionally indistinguishable from wildtype MscS. Thus, mutation of open-state lipid interacting residues does not differentially stabilize or destabilize the open, closed, intermediate, or transition states of MscS. Based on these results and other data from the literature, we propose a new gating paradigm for MscS where MscS acts as a "Jack-In-The-Box" with the intrinsic bilayer lateral pressure holding the channel in the closed state. In this model, upon application of extrinsic tension the channel springs into the open state due to relief of the intrinsic lipid bilayer pressure.

Original languageEnglish (US)
Pages (from-to)159-166
Number of pages8
JournalBiochimica et Biophysica Acta - General Subjects
Volume1848
Issue number1 Pt A
DOIs
StatePublished - Jan 1 2015

Fingerprint

Jacks
Lipids
Lipid bilayers
Lipid Bilayers
Hydrophobic and Hydrophilic Interactions
Alanine
Assays
Electrophysiology
Pressure
Mutation
Clamping devices
Hydrophobicity
Linings
Leucine
Escherichia coli
Experiments

Keywords

  • Bacterial ion channel
  • Gating mechanism
  • Jack-In-The-Box
  • Lipid interaction
  • Mechanosensitive channel of small conductance (MscS)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The mechanosensitive channel of small conductance (MscS) functions as a Jack-in-the box. / Malcolm, Hannah R.; Blount, Paul; Maurer, Joshua A.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1848, No. 1 Pt A, 01.01.2015, p. 159-166.

Research output: Contribution to journalArticle

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