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New insights of membrane environment effects on MscL channel mechanics from theoretical approaches
Author(s) -
Debret Gaëlle,
Valadié Hélène,
Stadler Andreas Maximilian,
Etchebest Catherine
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21810
Subject(s) - mechanosensitive channels , lipid bilayer , biophysics , molecular dynamics , chemical physics , chemistry , membrane , gating , periplasmic space , transmembrane protein , conductance , bilayer , ion channel , physics , computational chemistry , biology , escherichia coli , biochemistry , condensed matter physics , receptor , gene
The prokaryotic mechanosensitive channel of large conductance (MscL) is a remarkable integral membrane protein. During hypo‐osmotic shock, it responses to membrane tension through large conformational changes, that lead to an open state of the pore. The structure of the channel from Mycobacterium tuberculosis has been resolved in the closed state. Numerous experiments have attempted to trap the channel in its open state but they did not succeed in obtaining a structure. A gating mechanism has been proposed based on different experimental data but there is no experimental technique available to follow this process in atomic details. In addition, it has been shown that a decrease of the lipid bilayer thickness lowered MscL activation energy and stabilized a structurally distinct closed channel intermediate. Here, we use atomistic molecular dynamics simulations to investigate the effect of the lipid bilayer thinning on our model of the structure of the Escherichia coli. We thoroughly analyze simulations of the channel embedded in two pre‐equilibrated membranes differing by their hydrophobic tail length (DMPE and POPE). The MscL structure remains stable in POPE, whereas a distinct structural state is obtained in DMPE in response to hydrophobic mismatch. This latter is obtained by tilts and kinks of the transmembrane helices, leading to a widening and a diminution of the channel height. Part of these motions is guided by a competition between solvent and lipids for the interaction with the periplasmic loops. We finally conduct a principal component analysis of the simulation and compare anharmonic motions with harmonic ones, previously obtained from a coarse‐grained normal mode analysis performed on the same structural model. Significant similarities exist between low‐frequency harmonic motions and those observed with essential dynamics in DMPE. In summary, change in membrane thickness permits to accelerate the conformational changes involved in the mechanics of the E. coli channel, providing a closed structural intermediate en route to the open state. These results give clues for better understanding why the channel activation energy is lowered in a thinner membrane. Proteins 2008. © 2007 Wiley‐Liss, Inc.