TCB Publications - Abstract

Marcos Sotomayor, Trudy A. van der Straaten, Umberto Ravaioli, and Klaus Schulten. Electrostatic properties of the mechanosensitive channel of small conductance MscS. Biophysical Journal, 90:3496-3510, 2006. (PMC: 1440732)

SOTO2006 The mechanosensitive channel of small conductance (MscS) belongs to a family of membrane proteins that are gated in response to changes in membrane tension, thereby protecting the cell from hypo-osmotic shock. Here we report on passive ion transport simulations of MscS in a POPC bilayer using a coarse-grained particle-based description based on the Boltzmann transport Monte Carlo method. Single channel current-voltage curves are computed over hundreds of nanoseconds for channel conformations derived from all-atom molecular dynamics simulations reaching an overall simulation time of over 5 microseconds. Channel conformations similar to that of the crystal structure exhibit low conductance, whereas conformations reached after opening the channel by means of steered molecular dynamics simulations match experimentally determined conductances. However, while experiments indicate a slight preference for anionic currents, the simulated channel strongly selects anions over cations and direction of rectification at high voltages is opposite to what is observed in experiments. Three-dimensional maps of time-averaged ion distribution and equilibrium occupancy profiles constructed from trajectory data indicate separation of anions and cations inside and in the immediate vicinity of the large cytoplasmic domain of MscS, in accordance with earlier molecular dynamics simulations. This separation arises from the distribution of ionizable residues of MscS and suggests a specific, yet unknown, functional purpose.

Download Full Text

The manuscripts available on our site are provided for your personal use only and may not be retransmitted or redistributed without written permissions from the paper's publisher and author. You may not upload any of this site's material to any public server, on-line service, network, or bulletin board without prior written permission from the publisher and author. You may not make copies for any commercial purpose. Reproduction or storage of materials retrieved from this web site is subject to the U.S. Copyright Act of 1976, Title 17 U.S.C.

Download full text: PDF (707.2KB)