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Biophys J, May 2001, p. 2074-2081, Vol. 80, No. 5
Beckman Institute, Department of Physics, University of Illinois, 405 N. Mathews Avenue, Urbana, Illinois 61801 USA
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 Mycobacterium 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 totaling 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 least mobile 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.
Biophys J, May 2001, p. 2074-2081, Vol. 80, No. 5
© 2001 by the Biophysical Society 0006-3495/01/05/2074/08 $2.00
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