Simulation of MscL Gating in a bilayer under stress

The initial stages of the gating of the mechanoselective channel of
large conductance from Mycobacterium tuberculosis have been studied in
atomic detail using molecular dynamics simulation techniques. A
truncated form of the protein complex embedded in a
palmitoyloleoylphosphatidylcholine lipid bilayer and surrounded by
explicit water was simulated under different pressure conditions to
mimic the effects of tension and compression within the membrane on the
protein. As a direct result of lateral tension being applied to the
membrane, an increase in the tilt of a subset of the transmembrane
helices was observed. This in turn led to the enlargement of the pore
and the disruption of the hydrophobic gate consisting of residues Ile-14
and Val-21. The simulations suggest that opening occurs in a sequential
staged process. Such a mechanism could explain the partial opening or
staged conductance observed in patch-clamp experiments using related
large conductance mechanosensitive channel complexes.