Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Science Signaling

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 22 November 2002:
Vol. 298. no. 5598, pp. 1582 - 1587
DOI: 10.1126/science.1077945

Research Articles

Crystal Structure of Escherichia coli MscS, a Voltage-Modulated and Mechanosensitive Channel

Randal B. Bass,1 Pavel Strop,2 Margaret Barclay,3 Douglas C. Rees13*

The mechanosensitive channel of small conductance (MscS) responds both to stretching of the cell membrane and to membrane depolarization. The crystal structure at 3.9 angstroms resolution demonstrates that Escherichia coli MscS folds as a membrane-spanning heptamer with a large cytoplasmic region. Each subunit contains three transmembrane helices (TM1, -2, and -3), with the TM3 helices lining the pore, while TM1 and TM2, with membrane-embedded arginines, are likely candidates for the tension and voltage sensors. The transmembrane pore, apparently captured in an open state, connects to a large chamber, formed within the cytoplasmic region, that connects to the cytoplasm through openings that may function as molecular filters. Although MscS is likely to be structurally distinct from other ion channels, similarities in gating mechanisms suggest common structural elements.

1 Division of Chemistry and Chemical Engineering,
2 Biochemistry Option,
3 Howard Hughes Medical Institute, Mail Code 114-96, California Institute of Technology, Pasadena, CA 91125, USA.
*   To whom correspondence should be addressed. E-mail: dcrees{at}caltech.edu.


Read the Full Text



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
On the Structure of the N-Terminal Domain of the MscL Channel: Helical Bundle or Membrane Interface.
I. Iscla, R. Wray, and P. Blount (2008)
Biophys. J. 95, 2283-2291
   Abstract »    Full Text »    PDF »
The Structure of an Open Form of an E. coli Mechanosensitive Channel at 3.45 A Resolution.
W. Wang, S. S. Black, M. D. Edwards, S. Miller, E. L. Morrison, W. Bartlett, C. Dong, J. H. Naismith, and I. R. Booth (2008)
Science 321, 1179-1183
   Abstract »    Full Text »    PDF »
A Structural Mechanism for MscS Gating in Lipid Bilayers.
V. Vasquez, M. Sotomayor, J. Cordero-Morales, K. Schulten, and E. Perozo (2008)
Science 321, 1210-1214
   Abstract »    Full Text »    PDF »
Mechanosensitive Channel MscS in the Open State: Modeling of the Transition, Explicit Simulations, and Experimental Measurements of Conductance.
A. Anishkin, K. Kamaraju, and S. Sukharev (2008)
J. Gen. Physiol. 132, 67-83
   Abstract »    Full Text »    PDF »
Structure, Function, and Evolution of Bacterial ATP-Binding Cassette Systems.
A. L. Davidson, E. Dassa, C. Orelle, and J. Chen (2008)
Microbiol. Mol. Biol. Rev. 72, 317-364
   Abstract »    Full Text »    PDF »
Bubbles, Gating, and Anesthetics in Ion Channels.
R. Roth, D. Gillespie, W. Nonner, and R. E. Eisenberg (2008)
Biophys. J. 94, 4282-4298
   Abstract »    Full Text »    PDF »
Responses of Bacillus subtilis to Hypotonic Challenges: Physiological Contributions of Mechanosensitive Channels to Cellular Survival.
T. Hoffmann, C. Boiangiu, S. Moses, and E. Bremer (2008)
Appl. Envir. Microbiol. 74, 2454-2460
   Abstract »    Full Text »    PDF »
Pore Mutations of the Escherichia coli MscS Channel Affect Desensitization but Not Ionic Preference.
M. D. Edwards, W. Bartlett, and I. R. Booth (2008)
Biophys. J. 94, 3003-3013
   Abstract »    Full Text »    PDF »
Interaction between the Cytoplasmic and Transmembrane Domains of the Mechanosensitive Channel MscS.
T. Nomura, M. Sokabe, and K. Yoshimura (2008)
Biophys. J. 94, 1638-1645
   Abstract »    Full Text »    PDF »
Characterization of the Resting MscS: Modeling and Analysis of the Closed Bacterial Mechanosensitive Channel of Small Conductance.
A. Anishkin, B. Akitake, and S. Sukharev (2008)
Biophys. J. 94, 1252-1266
   Abstract »    Full Text »    PDF »
Structural basis for regulation of bifunctional roles in replication initiator protein.
A. Nakamura, C. Wada, and K. Miki (2007)
PNAS 104, 18484-18489
   Abstract »    Full Text »    PDF »
2,2,2-Trifluoroethanol Changes the Transition Kinetics and Subunit Interactions in the Small Bacterial Mechanosensitive Channel MscS.
B. Akitake, R. E. J. Spelbrink, A. Anishkin, J. A. Killian, B. de Kruijff, and S. Sukharev (2007)
Biophys. J. 92, 2771-2784
   Abstract »    Full Text »    PDF »
Molecular and electrophysiological characterization of a mechanosensitive channel expressed in the chloroplasts of Chlamydomonas.
Y. Nakayama, K. Fujiu, M. Sokabe, and K. Yoshimura (2007)
PNAS 104, 5883-5888
   Abstract »    Full Text »    PDF »
Ion Conduction through MscS as Determined by Electrophysiology and Simulation.
M. Sotomayor, V. Vasquez, E. Perozo, and K. Schulten (2007)
Biophys. J. 92, 886-902
   Abstract »    Full Text »    PDF »
Gain-of-Function Mutations in the MEC-4 DEG/ENaC Sensory Mechanotransduction Channel Alter Gating and Drug Blockade.
A. L. Brown, S. M. Fernandez-Illescas, Z. Liao, and M. B. Goodman (2007)
J. Gen. Physiol. 129, 161-173
   Abstract »    Full Text »    PDF »
Nanoliter microfluidic hybrid method for simultaneous screening and optimization validated with crystallization of membrane proteins.
L. Li, D. Mustafi, Q. Fu, V. Tereshko, D. L. Chen, J. D. Tice, and R. F. Ismagilov (2006)
PNAS 103, 19243-19248
   Abstract »    Full Text »    PDF »
Lipid-Protein Interaction of the MscS Mechanosensitive Channel Examined by Scanning Mutagenesis.
T. Nomura, M. Sokabe, and K. Yoshimura (2006)
Biophys. J. 91, 2874-2881
   Abstract »    Full Text »    PDF »
A limited universe of membrane protein families and folds..
A. Oberai, Y. Ihm, S. Kim, and J. U. Bowie (2006)
Protein Sci. 15, 1723-1734
   Abstract »    Full Text »    PDF »
Positioning of proteins in membranes: A computational approach..
A. L. Lomize, I. D. Pogozheva, M. A. Lomize, and H. I. Mosberg (2006)
Protein Sci. 15, 1318-1333
   Abstract »    Full Text »    PDF »
Voltage-Dependent Hydration and Conduction Properties of the Hydrophobic Pore of the Mechanosensitive Channel of Small Conductance.
S. A. Spronk, D. E. Elmore, and D. A. Dougherty (2006)
Biophys. J. 90, 3555-3569
   Abstract »    Full Text »    PDF »
Electrostatic Properties of the Mechanosensitive Channel of Small Conductance MscS.
M. Sotomayor, T. A. van der Straaten, U. Ravaioli, and K. Schulten (2006)
Biophys. J. 90, 3496-3510
   Abstract »    Full Text »    PDF »
Projection structure of the human copper transporter CTR1 at 6-A resolution reveals a compact trimer with a novel channel-like architecture.
S. G. Aller and V. M. Unger (2006)
PNAS 103, 3627-3632
   Abstract »    Full Text »    PDF »
Protein Complexes of the Escherichia coli Cell Envelope.
F. Stenberg, P. Chovanec, S. L. Maslen, C. V. Robinson, L. L. Ilag, G. von Heijne, and D. O. Daley (2005)
J. Biol. Chem. 280, 34409-34419
   Abstract »    Full Text »    PDF »
Transmembrane glycine zippers: Physiological and pathological roles in membrane proteins.
S. Kim, T.-J. Jeon, A. Oberai, D. Yang, J. J. Schmidt, and J. U. Bowie (2005)
PNAS 102, 14278-14283
   Abstract »    Full Text »    PDF »
Ion Transport through Membrane-Spanning Nanopores Studied by Molecular Dynamics Simulations and Continuum Electrostatics Calculations.
C. Peter and G. Hummer (2005)
Biophys. J. 89, 2222-2234
   Abstract »    Full Text »    PDF »
The structure of phospholamban pentamer reveals a channel-like architecture in membranes.
K. Oxenoid and J. J. Chou (2005)
PNAS 102, 10870-10875
   Abstract »    Full Text »    PDF »
Surface Changes of the Mechanosensitive Channel MscS upon Its Activation, Inactivation, and Closing.
W. Grajkowski, A. Kubalski, and P. Koprowski (2005)
Biophys. J. 88, 3050-3059
   Abstract »    Full Text »    PDF »
Lactococcus lactis Uses MscL as Its Principal Mechanosensitive Channel.
J. H. A. Folgering, P. C. Moe, G. K. Schuurman-Wolters, P. Blount, and B. Poolman (2005)
J. Biol. Chem. 280, 8784-8792
   Abstract »    Full Text »    PDF »
NMR Structure of Mistic, a Membrane-Integrating Protein for Membrane Protein Expression.
T. P. Roosild, J. Greenwald, M. Vega, S. Castronovo, R. Riek, and S. Choe (2005)
Science 307, 1317-1321
   Abstract »    Full Text »    PDF »
Membrane-Protein Interactions in Mechanosensitive Channels.
P. Wiggins and R. Phillips (2005)
Biophys. J. 88, 880-902
   Abstract »    Full Text »    PDF »
The Transmembrane Domain of the Acetylcholine Receptor: Insights from Simulations on Synthetic Peptide Models.
L. Saiz and M. L. Klein (2005)
Biophys. J. 88, 959-970
   Abstract »    Full Text »    PDF »
The "Dashpot" Mechanism of Stretch-dependent Gating in MscS.
B. Akitake, A. Anishkin, and S. Sukharev (2005)
J. Gen. Physiol. 125, 143-154
   Abstract »    Full Text »    PDF »
Gain-of-function Mutations Reveal Expanded Intermediate States and a Sequential Action of Two Gates in MscL.
A. Anishkin, C.-S. Chiang, and S. Sukharev (2005)
J. Gen. Physiol. 125, 155-170
   Abstract »    Full Text »    PDF »
A quantitative assessment of models for voltage-dependent gating of ion channels.
M. Grabe, H. Lecar, Y. N. Jan, and L. Y. Jan (2004)
PNAS 101, 17640-17645
   Abstract »    Full Text »    PDF »
Eukaryotic CTR Copper Uptake Transporters Require Two Faces of the Third Transmembrane Domain for Helix Packing, Oligomerization, and Function.
S. G. Aller, E. T. Eng, C. J. De Feo, and V. M. Unger (2004)
J. Biol. Chem. 279, 53435-53441
   Abstract »    Full Text »    PDF »
Helicobacter pylori Vacuolating Cytotoxin, VacA, Is Responsible for Gastric Ulceration.
A. Wada, E. Yamasaki, and T. Hirayama (2004)
J. Biochem. 136, 741-746
   Abstract »    Full Text »    PDF »
Molecular Dynamics Study of Gating in the Mechanosensitive Channel of Small Conductance MscS.
M. Sotomayor and K. Schulten (2004)
Biophys. J. 87, 3050-3065
   Abstract »    Full Text »    PDF »
Genetic Models of Mechanotransduction: The Nematode Caenorhabditis elegans.
P. Syntichaki and N. Tavernarakis (2004)
Physiol Rev 84, 1097-1153
   Abstract »    Full Text »    PDF »
NMR Solution Structure of Ole e 6, a Major Allergen from Olive Tree Pollen.
M. A. Trevino, M. F. Garcia-Mayoral, P. Barral, M. Villalba, J. Santoro, M. Rico, R. Rodriguez, and M. Bruix (2004)
J. Biol. Chem. 279, 39035-39041
   Abstract »    Full Text »    PDF »
Computational analysis of {alpha}-helical membrane protein structure: implications for the prediction of 3D structural models.
T. A. Eyre, L. Partridge, and J. M. Thornton (2004)
Protein Eng. Des. Sel. 17, 613-624
   Abstract »    Full Text »    PDF »
Gating Transitions in Bacterial Ion Channels Measured at 3 {micro}s Resolution.
G. Shapovalov and H. A. Lester (2004)
J. Gen. Physiol. 124, 151-161
   Abstract »    Full Text »    PDF »
Mechanosensitive ion channels: molecules of mechanotransduction.
B. Martinac (2004)
J. Cell Sci. 117, 2449-2460
   Abstract »    Full Text »    PDF »
Water Dynamics and Dewetting Transitions in the Small Mechanosensitive Channel MscS.
A. Anishkin and S. Sukharev (2004)
Biophys. J. 86, 2883-2895
   Abstract »    Full Text »    PDF »
Membrane channel structure of Helicobacter pylori vacuolating toxin: Role of multiple GXXXG motifs in cylindrical channels.
S. Kim, A. K. Chamberlain, and J. U. Bowie (2004)
PNAS 101, 5988-5991
   Abstract »    Full Text »    PDF »
Total chemical synthesis and electrophysiological characterization of mechanosensitive channels from Escherichia coli and Mycobacterium tuberculosis.
D. Clayton, G. Shapovalov, J. A. Maurer, D. A. Dougherty, H. A. Lester, and G. G. Kochendoerfer (2004)
PNAS 101, 4764-4769
   Abstract »    Full Text »    PDF »
From the Cover: Computational design of water-soluble analogues of the potassium channel KcsA.
A. M. Slovic, H. Kono, J. D. Lear, J. G. Saven, and W. F. DeGrado (2004)
PNAS 101, 1828-1833
   Abstract »    Full Text »    PDF »
Mechanosensitive Channels: Multiplicity of Families and Gating Paradigms.
S. Sukharev and D. P. Corey (2004)
Sci. STKE 2004, re4
   Abstract »    Full Text »    PDF »
A role for mechanosensitive channels in survival of stationary phase: Regulation of channel expression by RpoS.
N. R. Stokes, H. D. Murray, C. Subramaniam, R. L. Gourse, P. Louis, W. Bartlett, S. Miller, and I. R. Booth (2003)
PNAS 100, 15959-15964
   Abstract »    Full Text »    PDF »
Use of thiol-disulfide equilibria to measure the energetics of assembly of transmembrane helices in phospholipid bilayers.
L. Cristian, J. D. Lear, and W. F. DeGrado (2003)
PNAS 100, 14772-14777
   Abstract »    Full Text »    PDF »
An Isothermal Titration Calorimetry Study on the Binding of Four Volatile General Anesthetics to the Hydrophobic Core of a Four-{alpha}-Helix Bundle Protein.
T. Zhang and J. S. Johansson (2003)
Biophys. J. 85, 3279-3285
   Abstract »    Full Text »    PDF »
Gating of MscL Studied by Steered Molecular Dynamics.
J. Gullingsrud and K. Schulten (2003)
Biophys. J. 85, 2087-2099
   Abstract »    Full Text »    PDF »
The Closed Structure of the MscS Mechanosensitive Channel: CROSS-LINKING OF SINGLE CYSTEINE MUTANTS.
S. Miller, M. D. Edwards, C. Ozdemir, and I. R. Booth (2003)
J. Biol. Chem. 278, 32246-32250
   Abstract »    Full Text »    PDF »
The Motility of Mollicutes.
C. W. Wolgemuth, O. Igoshin, and G. Oster (2003)
Biophys. J. 85, 828-842
   Abstract »    Full Text »    PDF »
Liquid-vapor oscillations of water in hydrophobic nanopores.
O. Beckstein and M. S. P. Sansom (2003)
PNAS 100, 7063-7068
   Abstract »    Full Text »    PDF »
The transient receptor potential channel on the yeast vacuole is mechanosensitive.
X.-L. Zhou, A. F. Batiza, S. H. Loukin, C. P. Palmer, C. Kung, and Y. Saimi (2003)
PNAS 100, 7105-7110
   Abstract »    Full Text »    PDF »
Structure and assembly of an augmented Sm-like archaeal protein 14-mer.
C. Mura, M. Phillips, A. Kozhukhovsky, and D. Eisenberg (2003)
PNAS 100, 4539-4544
   Abstract »    Full Text »    PDF »
C Termini of the Escherichia coli Mechanosensitive Ion Channel (MscS) Move Apart upon the Channel Opening.
P. Koprowski and A. Kubalski (2003)
J. Biol. Chem. 278, 11237-11245
   Abstract »    Full Text »    PDF »



ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)