Justin Gullingsrud, Dorina Kosztin, and Klaus Schulten.
Structural determinants of MscL gating studied by molecular
dynamics simulations.
Biophysical Journal, 80:2074-2081, 2001.
(PMC: 1301400)
GULL2001
The mechanosensitive channel of large conductance (MscL) in prokaryotes plays a crucial role in exocytosis as well as in the response to osmotic downshock. The channel can be gated by tension in the membrane bilayer. The determination of functionally important residues in MscL, patch-clamp studies of pressure-conductance relationships, and the recently elucidated crystal structure of MscL from Mycobaterium
tuberculosis, have guided the search for the mechanism of MscL gating. Here, we present a molecular dynamics study of the MscL protein embedded in a fully hydrated POPC bilayer. Simulations totalling 3 ns in length were carried out under conditions of constant temperature and pressure using periodic boundary conditions and full electrostatics. The protein remained in the closed state corresponding to the crystal structure, as evidenced by its impermeability to
water. Analysis of equilibrium fluctuations showed that the protein was most immobile in the narrowest part of the channel. The gating process was investigated through simulations of the bare protein under conditions of constant surface tension. Under a range of conditions the transmembrane helices flattened as the pore widened. Implications for the gating mechanism in light of these and experimental results are discussed.
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