CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING |
Gating of the mechanosensitive channel protein MscL: The interplay of membrane and protein
Jonggu Jeon 1 and Gregory A. Voth 1*
1 University of Utah
* To whom correspondence should be addressed. E-mail: voth{at}chem.utah.edu.
Submitted on March 29, 2007
Revised on May 4, 2007
Accepted on 21 December 2007
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Abstract |
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The mechanosensitive channel of large conductance (MscL) belongs to a family of transmembrane channel proteins in bacteria and functions as a safety valve that relieves the turgor pressure produced by the osmotic down-shock. MscL gating can be triggered solely by the stretch of membrane. This work reports an effort to understand this mechanotransduction by means of molecular dynamics (MD) simulation on the MscL of mycobacterium tuberculosis (Tb-MscL) embedded in a palmitoyloleoylphosphatidylethanolamine (POPE) membrane. The equilibrium MD under zero membrane tension produced a more compact protein structure, as measured by its radii of gyration, compared to the crystal structure, in agreement with previous experimental findings. Even under a large applied tension up to 1000 dyn/cm, the MscL lateral dimension largely remained unchanged after up to 20 ns of simulation. A nonequilibrium MD simulation of 3% membrane expansion showed a significant increase in the membrane rigidity upon MscL inclusion, which can contribute to efficient mechanotransduction. Direct observation of channel opening was possible only when an explicit lateral bias force was applied to each of the 5 subunits of MscL in the radially outward direction. With this, open structures with large pore of 10 Å radius could be obtained. The channel opening takes place in a stepwise manner and is concurrent with the water chain formation across the channel. The N-terminal S1 helices stabilize the open structure and the membrane asymmetry (different lipid density on the two leaflets of membrane) promotes the channel opening. It is also found that the water chain formation takes place without direct involvement of protein hydrophilic residues.
Key Words:
ion channel, mechanosensitive channel, mechanotransduction, membrane elasticity, molecular dynamics simulation, protein-membrane interaction
