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Science 321 (5893): 1210-1214

Copyright © 2008 by the American Association for the Advancement of Science

A Structural Mechanism for MscS Gating in Lipid Bilayers

Valeria Vásquez,1,2 Marcos Sotomayor,3 Julio Cordero-Morales,1,2 Klaus Schulten,4 Eduardo Perozo2*

Abstract: The mechanosensitive channel of small conductance (MscS) is a key determinant in the prokaryotic response to osmotic challenges. We determined the structural rearrangements associated with MscS activation in membranes, using functorial measurements, electron paramagnetic resonance spectroscopy, and computational analyses. MscS was trapped in its open conformation after the transbilayer pressure profile was modified through the asymmetric incorporation of lysophospholipids. The transition from the closed to the open state is accompanied by the downward tilting of the transmembrane TM1-TM2 hairpin and by the expansion, tilt, and rotation of the TM3 helices. These movements expand the permeation pathway, leading to an increase in accessibility to water around TM3. Our open MscS model is compatible with single-channel conductance measurements and supports the notion that helix tilting is associated with efficient pore widening in mechanosensitive channels.

1 Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
2 Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA.
3 Howard Hughes Medical Institute and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
4 Department of Physics, University of Illinois at Urbana–Champaign, and Beckman Institute for Advanced Science and Technology, Urbana, IL 61801, USA.

* To whom correspondence should be addressed. E-mail: eperozo{at}uchicago.edu


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