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 Perozo^2*

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

MscS-Like10 is a stretch-activated ion channel from Arabidopsis thaliana with a preference for anions.

G. Maksaev and E. S. Haswell (2012)
PNAS 109, 19015-19020
 |  Abstract »  |  Full Text »  |  PDF »

Structure and molecular mechanism of an anion-selective mechanosensitive channel of small conductance.

X. Zhang, J. Wang, Y. Feng, J. Ge, W. Li, W. Sun, I. Iscla, J. Yu, P. Blount, Y. Li, et al. (2012)
PNAS 109, 18180-18185
 |  Abstract »  |  Full Text »  |  PDF »

Conformational state of the MscS mechanosensitive channel in solution revealed by pulsed electron-electron double resonance (PELDOR) spectroscopy.

C. Pliotas, R. Ward, E. Branigan, A. Rasmussen, G. Hagelueken, H. Huang, S. S. Black, I. R. Booth, O. Schiemann, and J. H. Naismith (2012)
PNAS 109, E2675-E2682
 |  Abstract »  |  Full Text »  |  PDF »

Insight into DEG/ENaC Channel Gating from Genetics and Structure.

A. L. Eastwood and M. B. Goodman (2012)
Physiology 27, 282-290
 |  Abstract »  |  Full Text »  |  PDF »

The MscS and MscL Families of Mechanosensitive Channels Act as Microbial Emergency Release Valves.

I. R. Booth and P. Blount (2012)
J. Bacteriol. 194, 4802-4809
 |  Abstract »  |  Full Text »  |  PDF »

Molecular force transduction by ion channels - diversity and unifying principles.

S. Sukharev and F. Sachs (2012)
J. Cell Sci. 125, 3075-3083
 |  Abstract »  |  Full Text »  |  PDF »

Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS.

T. Nomura, C. G. Cranfield, E. Deplazes, D. M. Owen, A. Macmillan, A. R. Battle, M. Constantine, M. Sokabe, and B. Martinac (2012)
PNAS 109, 8770-8775
 |  Abstract »  |  Full Text »  |  PDF »

Signaling by Sensory Receptors.

D. Julius and J. Nathans (2012)
Cold Spring Harb Perspect Biol 4, a005991
 |  Abstract »  |  Full Text »  |  PDF »

Expression and characterization of the bacterial mechanosensitive channel MscS in Xenopus laevis oocytes.

G. Maksaev and E. S. Haswell (2011)
J. Gen. Physiol. 138, 641-649
 |  Abstract »  |  Full Text »  |  PDF »

The pathway and spatial scale for MscS inactivation.

K. Kamaraju, V. Belyy, I. Rowe, A. Anishkin, and S. Sukharev (2011)
J. Gen. Physiol. 138, 49-57
 |  Abstract »  |  Full Text »  |  PDF »

Specificity of Intramembrane Protein-Lipid Interactions.

F.-X. Contreras, A. M. Ernst, F. Wieland, and B. Brugger (2011)
Cold Spring Harb Perspect Biol 3, a004705
 |  Abstract »  |  Full Text »  |  PDF »

Lipid Simulations: A Perspective on Lipids in Action.

I. Vattulainen and T. Rog (2011)
Cold Spring Harb Perspect Biol 3, a004655
 |  Abstract »  |  Full Text »  |  PDF »

Genetic Screen for Potassium Leaky Small Mechanosensitive Channels (MscS) in Escherichia coli: RECOGNITION OF CYTOPLASMIC {beta} DOMAIN AS A NEW GATING ELEMENT.

P. Koprowski, W. Grajkowski, E. Y. Isacoff, and A. Kubalski (2011)
J. Biol. Chem. 286, 877-888
 |  Abstract »  |  Full Text »  |  PDF »

An improved open-channel structure of MscL determined from FRET confocal microscopy and simulation.

B. Corry, A. C. Hurst, P. Pal, T. Nomura, P. Rigby, and B. Martinac (2010)
J. Gen. Physiol. 136, 483-494
 |  Abstract »  |  Full Text »  |  PDF »

Mechanosensitivity of ion channels based on protein-lipid interactions.

K. Yoshimura and M. Sokabe (2010)
J R Soc Interface 7, S307-S320
 |  Abstract »  |  Full Text »  |  PDF »

Tryptophan in the Pore of the Mechanosensitive Channel MscS: ASSESSMENT OF PORE CONFORMATIONS BY FLUORESCENCE SPECTROSCOPY.

T. Rasmussen, M. D. Edwards, S. S. Black, A. Rasmussen, S. Miller, and I. R. Booth (2010)
J. Biol. Chem. 285, 5377-5384
 |  Abstract »  |  Full Text »  |  PDF »

Dynamic aspects of functioning membrane proteins.

Y. Kubo and E. Y. Isacoff (2009)
J. Physiol. 587, 5315-5316
 |  Full Text »  |  PDF »

State-stabilizing Interactions in Bacterial Mechanosensitive Channel Gating and Adaptation.

A. Anishkin and S. Sukharev (2009)
J. Biol. Chem. 284, 19153-19157
 |  Abstract »  |  Full Text »  |  PDF »

HIGHLIGHTS FROM THE LITERATURE.

(2008)
Physiology 23, 310-312
 |  Full Text »  |  PDF »

BIOCHEMISTRY: Opening the Molecular Floodgates.

C. S. Gandhi and D. C. Rees (2008)
Science 321, 1166-1167
 |  Abstract »  |  Full Text »  |  PDF »