Protein Gating

Although secondary structure changes of proteins can not be modelled  in Martini, tertiary conformational changes are unrestricted and in principle realistic within the general approximations underlying the coarse-grained model.

mscl-haloA fine example is the gating process of the mechano-sensitive channel of large conductance, MscL. Both the wild-type Tb-MscL and its gain-of-function mutant V21D embedded in a solvated lipid bilayer have been simulated [1].  Putting the membrane under tension, the channels undergo significant conformational changes in accordance with an iris-like expansion mechanism, reaching a conducting state on a microsecond timescale. The most pronounced expansion of the pore has been observed for the V21D mutant, which is consistent with the experimentally shown gain-of-function phenotype of the V21D mutant. Due to the inhomogeneous pressure distribution around the protein [5], the mere shape change of the channel provides a large contribution to the gating energy [6]. The gating of a MscL channel embedded in a liposome has also been simulated [4] (see figure). Other channel proteins that have been simulated with Martini include voltage-gated potassium channels [2] and the SecY channel [3].

  • [1] S. Yefimov, P.R. Onck, E. van der Giessen, S.J. Marrink. Mechanosensitive membrane channels in action. Biophys. J., 94:2994-3002, 2008.
  • [2] W. Treptow, S.J. Marrink, M. Tarek. Gating motions in voltage-gated potassium channels revealed by coarse-grained molecular dynamics simulations. JPC-B, 112:3277-3282, 2008.
  • [3] J.A. Lycklama a Nijeholt, M. Bulacu, S.J. Marrink, A.J.M. Driessen. Immobilization of the plug domain inside the SecY channel allows unrestricted protein translocation. J. Biol. Chem., 285:23747-23754, 2010.
  • [4] M. Louhivuori, H.J. Risselada, E. van der Giessen, S.J. Marrink. Release of content through mechano-sensitive gates in pressurized liposomes. PNAS, 107:19856-19860, 2010. open access
  • [5] O.H.S. Ollila, H.J. Risselada, M. Louhivuori, E. Lindahl, I. Vattulainen, S.J. Marrink. 3D Pressure distribution in lipid membranes and membrane-protein complexes. Phys. Rev. Lett., 102:078101, 2009.
  • [6] O.H.S. Ollila, M. Louhivuori, S.J. Marrink, I. Vattulainen. Protein shape change has a major effect on the gating energy of a mechanosensitive channel. Biophys. J., 100:1651-1659, 2011.