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Molecular Architecture of the KvAP Voltage-Dependent K+ Channel in a Lipid Bilayer
Luis G. Cuello,D. Marien Cortes,Eduardo Perozo*
We have analyzed the local structure and dynamics of the prokaryoticvoltage-dependent K+ channel (KvAP) at 0 millivolts, using site-directedspin labeling and electron paramagnetic resonance spectroscopy.We show that the S4 segment is located at the protein/lipidinterface, with most of its charges protected from the lipidenvironment. Structurally, S4 is highly dynamic and is separatedinto two short helices by a flexible linker. Accessibility anddynamics data indicate that the S1 segment is surrounded byother parts of the protein. We propose that S1 is at the contactinterface between the voltage-sensing and pore domains. Theseresults establish the general principles of voltage-dependentchannel structure in a biological membrane.
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22906, USA.
* To whom correspondence should be addressed. E-mail: eperozo{at}virginia.edu
Mapping the Membrane-aqueous Border for the Voltage-sensing Domain of a Potassium Channel.
E. J. Neale, H. Rong, C. J. Cockcroft, and A. Sivaprasadarao (2007)
J. Biol. Chem.
282, 37597-37604
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Tarantula Toxins Interact with Voltage Sensors within Lipid Membranes.
M. Milescu, J. Vobecky, S. H. Roh, S. H. Kim, H. J. Jung, J. I. Kim, and K. J. Swartz (2007)
J. Gen. Physiol.
130, 497-511
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Essential, Completely Conserved Glycine Residue in the Domain III S2 S3 Linker of Voltage-gated Calcium Channel {alpha}1 Subunits in Yeast and Mammals.
K. Iida, J. Teng, T. Tada, A. Saka, M. Tamai, H. Izumi-Nakaseko, S. Adachi-Akahane, and H. Iida (2007)
J. Biol. Chem.
282, 25659-25667
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APETx1 from Sea Anemone Anthopleura elegantissima Is a Gating Modifier Peptide Toxin of the Human Ether-a-go-go- Related Potassium Channel.
M. Zhang, X.-S. Liu, S. Diochot, M. Lazdunski, and G.-N. Tseng (2007)
Mol. Pharmacol.
72, 259-268
|Abstract »|Full Text »|PDF »
A hydrophobic element secures S4 voltage sensor in position in resting Shaker K+ channels.
Contribution of hydrophobic and electrostatic interactions to the membrane integration of the Shaker K+ channel voltage sensor domain.
L. Zhang, Y. Sato, T. Hessa, G. von Heijne, J.-K. Lee, I. Kodama, M. Sakaguchi, and N. Uozumi (2007)
PNAS
104, 8263-8268
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Electron Paramagnetic Resonance Spectroscopy of Site-directed Spin Labels Reveals the Structural Heterogeneity in the N-terminal Domain of ApoA-I in Solution.
J. O. Lagerstedt, M. S. Budamagunta, M. N. Oda, and J. C. Voss (2007)
J. Biol. Chem.
282, 9143-9149
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On the thermodynamic stability of a charged arginine side chain in a transmembrane helix.
The I-II Loop Controls Plasma Membrane Expression and Gating of Cav3.2 T-Type Ca2+ Channels: A Paradigm for Childhood Absence Epilepsy Mutations.
I. Vitko, I. Bidaud, J. M. Arias, A. Mezghrani, P. Lory, and E. Perez-Reyes (2007)
J. Neurosci.
27, 322-330
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Size Matters: Erythromelalgia Mutation S241T in Nav1.7 Alters Channel Gating.
A. Lampert, S. D. Dib-Hajj, L. Tyrrell, and S. G. Waxman (2006)
J. Biol. Chem.
281, 36029-36035
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Distance measurements reveal a common topology of prokaryotic voltage-gated ion channels in the lipid bilayer.
J. Richardson, R. Blunck, P. Ge, P. R. Selvin, F. Bezanilla, D. M. Papazian, and A. M. Correa (2006)
PNAS
103, 15865-15870
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Molecular Template for a Voltage Sensor in a Novel K+ Channel. I. Identification and Functional Characterization of KvLm, a Voltage-gated K+ Channel from Listeria monocytogenes.
J. S. Santos, A. Lundby, C. Zazueta, and M. Montal (2006)
J. Gen. Physiol.
128, 283-292
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Molecular Template for a Voltage Sensor in a Novel K+ Channel. II. Conservation of a Eukaryotic Sensor Fold in a Prokaryotic K+ Channel.
A. Lundby, J. S. Santos, C. Zazueta, and M. Montal (2006)
J. Gen. Physiol.
128, 293-300
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Molecular Rearrangements of the Kv2.1 Potassium Channel Termini Associated with Voltage Gating.
E. Kobrinsky, L. Stevens, Y. Kazmi, D. Wray, and N. M. Soldatov (2006)
J. Biol. Chem.
281, 19233-19240
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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
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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
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Voltage sensor conformations in the open and closed states in ROSETTA structural models of K+ channels.
V. Yarov-Yarovoy, D. Baker, and W. A. Catterall (2006)
PNAS
103, 7292-7297
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Environment of the Gating Charges in the Kv1.2 Shaker Potassium Channel.
Differential Roles of S6 Domain Hinges in the Gating of KCNQ Potassium Channels.
G. Seebohm, N. Strutz-Seebohm, O. N. Ureche, R. Baltaev, A. Lampert, G. Kornichuk, K. Kamiya, T. V. Wuttke, H. Lerche, M. C. Sanguinetti, et al. (2006)
Biophys. J.
90, 2235-2244
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The Intrinsic Flexibility of the Kv Voltage Sensor and Its Implications for Channel Gating.
Z. A. Sands, A. Grottesi, and M. S. P. Sansom (2006)
Biophys. J.
90, 1598-1606
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Structural Analysis of a HAMP Domain: THE LINKER REGION OF THE PHOTOTRANSDUCER IN COMPLEX WITH SENSORY RHODOPSIN II.
E. Bordignon, J. P. Klare, M. Doebber, A. A. Wegener, S. Martell, M. Engelhard, and H.-J. Steinhoff (2005)
J. Biol. Chem.
280, 38767-38775
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Transient outward potassium current, 'Ito', phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms.
Transmembrane S1 Mutations in CNGA3 from Achromatopsia 2 Patients Cause Loss of Function and Impaired Cellular Trafficking of the Cone CNG Channel.
K. A. Patel, K. M. Bartoli, R. A. Fandino, A. N. Ngatchou, G. Woch, J. Carey, and J. C. Tanaka (2005)
Invest. Ophthalmol. Vis. Sci.
46, 2282-2290
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Functionally Active T1-T1 Interfaces Revealed by the Accessibility of Intracellular Thiolate Groups in Kv4 Channels.
G. Wang, M. Shahidullah, C. A. Rocha, C. Strang, P. J. Pfaffinger, and M. Covarrubias (2005)
J. Gen. Physiol.
126, 55-69
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Transmembrane helix prediction: a comparative evaluation and analysis.
J. M. Cuthbertson, D. A. Doyle, and M. S.P. Sansom (2005)
Protein Eng. Des. Sel.
18, 295-308
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Microbial K+ Channels.
S. H. Loukin, M. M.-C. Kuo, X.-L. Zhou, W. J. Haynes, C. Kung, and Y. Saimi (2005)
J. Gen. Physiol.
125, 521-527
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Molecular Compatibility of the Channel Gate and the N Terminus of S5 Segment for Voltage-gated Channel Activity.
M. Caprini, M. Fava, P. Valente, G. Fernandez-Ballester, C. Rapisarda, S. Ferroni, and A. Ferrer-Montiel (2005)
J. Biol. Chem.
280, 18253-18264
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The human Kv1.1 channel is palmitoylated, modulating voltage sensing: Identification of a palmitoylation consensus sequence.
R. A. Gubitosi-Klug, D. J. Mancuso, and R. W. Gross (2005)
PNAS
102, 5964-5968
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Differential Role of the {alpha}1C Subunit Tails in Regulation of the Cav1.2 Channel by Membrane Potential, {beta} Subunits, and Ca2+ Ions.
E. Kobrinsky, S. Tiwari, V. A. Maltsev, J. B. Harry, E. Lakatta, D. R. Abernethy, and N. M. Soldatov (2005)
J. Biol. Chem.
280, 12474-12485
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A fluorescent probe designed for studying protein conformational change.
B. E. Cohen, A. Pralle, X. Yao, G. Swaminath, C. S. Gandhi, Y. N. Jan, B. K. Kobilka, E. Y. Isacoff, and L. Y. Jan (2005)
PNAS
102, 965-970
|Abstract »|Full Text »|PDF »
A quantitative assessment of models for voltage-dependent gating of ion channels.