The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels.

Navid Bavi,D Marien Cortes,Pavel Strop,Adam P Hill,Douglas Rees,Joachim W Deitmer,Omid Bavi,Charles D Cox,Ben Corry,Paul R Rohde,Boris Martinac,Eduardo Perozo,Weihong Liu

doi:10.1038/ncomms11984

Abstract

The bacterial mechanosensitive channel MscL gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer. MscL represents an excellent model system to study the basic biophysical principles of mechanosensory transduction. However, understanding of the essential structural components that transduce bilayer tension into channel gating remains incomplete. Here using multiple experimental and computational approaches, we demonstrate that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane. We propose that this may also represent a common principle in the gating cycle of unrelated mechanosensitive ion channels, allowing the coupling of channel conformation to membrane dynamics.

Highlights

The bacterial mechanosensitive channel Mechanosensitive channels (MSs) channel of large conductance (MscL) gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer
Our data suggest that the gating mechanism of MscL, a primordial MS, might reveal a unifying fundamental blueprint that underlies the mechanosensitivity of structurally unrelated ion channels
Here we have fully investigated the role of the amphipathic N-terminal helix in the gating cycle of E. coli MscL

Summary

Introduction

The bacterial mechanosensitive channel MscL gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer. Using multiple experimental and computational approaches, we demonstrate that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane. We propose that this may represent a common principle in the gating cycle of unrelated mechanosensitive ion channels, allowing the coupling of channel conformation to membrane dynamics. Our data suggest that the gating mechanism of MscL, a primordial MS, might reveal a unifying fundamental blueprint that underlies the mechanosensitivity of structurally unrelated ion channels

Methods

Results

Conclusion