EurekaMag.com logo
+ Site Statistics
References:
53,623,987
Abstracts:
29,492,080
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

The gating mechanism of the bacterial mechanosensitive channel MscL revealed by molecular dynamics simulations: from tension sensing to channel opening



The gating mechanism of the bacterial mechanosensitive channel MscL revealed by molecular dynamics simulations: from tension sensing to channel opening



Channels 6(4): 317-331



One of the ultimate goals of the study on mechanosensitive (MS) channels is to understand the biophysical mechanisms of how the MS channel protein senses forces and how the sensed force induces channel gating. The bacterial MS channel MscL is an ideal subject to reach this goal owing to its resolved 3D protein structure in the closed state on the atomic scale and large amounts of electrophysiological data on its gating kinetics. However, the structural basis of the dynamic process from the closed to open states in MscL is not fully understood. In this study, we performed molecular dynamics (MD) simulations on the initial process of MscL opening in response to a tension increase in the lipid bilayer. To identify the tension-sensing site(s) in the channel protein, we calculated interaction energy between membrane lipids and candidate amino acids (AAs) facing the lipids. We found that Phe78 has a conspicuous interaction with the lipids, suggesting that Phe78 is the primary tension sensor of MscL. Increased membrane tension by membrane stretch dragged radially the inner (TM1) and outer (TM2) helices of MscL at Phe78, and the force was transmitted to the pentagon-shaped gate that is formed by the crossing of the neighboring TM1 helices in the inner leaflet of the bilayer. The radial dragging force induced radial sliding of the crossing portions, leading to a gate expansion. Calculated energy for this expansion is comparable to an experimentally estimated energy difference between the closed and the first subconductance state, suggesting that our model simulates the initial step toward the full opening of MscL. The model also successfully mimicked the behaviors of a gain of function mutant (G22N) and a loss of function mutant (F78N), strongly supporting that our MD model did simulate some essential biophysical aspects of the mechano-gating in MscL.

(PDF emailed within 0-6 h: $19.90)

Accession: 056350462

Download citation: RISBibTeXText

PMID: 23146938

DOI: 10.4161/chan.21895



Related references

Molecular mechanism on the gating of bacterial mechanosensitive channel MscL. Cell Structure & Function 26(5): 404, October, 2001

Gating of the mechanosensitive channel MscL studied by Steered Molecular Dynamics. Biophysical Journal 84(2 Part 2): 21a, February, 2003

Molecular dissection of the large mechanosensitive ion channel (MscL) of E. coli: Mutants with altered channel gating and pressure sensitivity. Journal of Membrane Biology 157(1): 17-25, 1997

Investigating lipid composition effects on the mechanosensitive channel of large conductance (MscL) using molecular dynamics simulations. Biophysical Journal 85(3): 1512-1524, 2003

Gating the bacterial mechanosensitive channel MscL invivo. Proceedings of the National Academy of Sciences of the United States of America 99(8): 5643-5648, 2002

The gating mechanism of the large mechanosensitive channel MscL. Nature 409(6821): 720-724, 2001

The activation mode of the mechanosensitive ion channel, MscL, by lysophosphatidylcholine differs from tension-induced gating. Faseb Journal 28(10): 4292-4302, 2015

Mechanosensitive behavior of bacterial cyclic nucleotide gated (bCNG) ion channels: Insights into the mechanism of channel gating in the mechanosensitive channel of small conductance superfamily. Biochemical and Biophysical Research Communications 417(3): 972-976, 2012

A peptide model of the mechanosensitive channel MscL investigated by molecular dynamics simulations and solid state nuclear magnetic resonance. European Biophysics Journal 32(3): 280, June, 2003

Molecular dynamics study on protein-water interplay in the mechanogating of the bacterial mechanosensitive channel MscL. European Biophysics Journal 44(7): 531-543, 2016

On the role of the S1-M1 linker in the gating mechanism of the large mechanosensitive channel MscL. Biophysical Journal 80(1 Part 2): 110a, January, 2001

Open channel of structure of MscL and the gating mechanism of mechanosensitive channels. Nature 418(6901): 2-8, 2002

Molecular dynamics simulations investigate the mechanism of Psalmotoxin 1 regulating gating process of an acid-sensing ion channel 1a at pH 5.5. Journal of Biomolecular Structure & Dynamics 36(10): 2558-2566, 2017

Energetic and spatial parameters for gating of the bacterial large conductance mechanosensitive channel, MscL. Journal of General Physiology 113(4): 525-540, 1999

Molecular simulations of the large conductance mechanosensitive (MscL) channel under mechanical loading. FEBS Letters 512(1-3): 185-190, 2002