scholarly journals The S4 Voltage Sensor Packs Against the Pore Domain in the KAT1 Voltage-Gated Potassium Channel

Neuron ◽  
2005 ◽  
Vol 47 (3) ◽  
pp. 395-406 ◽  
Author(s):  
Helen C. Lai ◽  
Michael Grabe ◽  
Yuh Nung Jan ◽  
Lily Yeh Jan
Keyword(s):  
Potassium Channel ◽  
Voltage Sensor ◽  
Voltage Gated ◽  
Pore Domain

scholarly journals Coupled Motions between Pore and Voltage-Sensor Domains: A Model for Shaker B, a Voltage-Gated Potassium Channel

2004 ◽  
Vol 87 (4) ◽  
pp. 2365-2379 ◽  
Author(s):  
Werner Treptow ◽  
Bernard Maigret ◽  
Christophe Chipot ◽  
Mounir Tarek
Keyword(s):  
Potassium Channel ◽  
Voltage Sensor ◽  
Voltage Gated

scholarly journals Pursuing the voltage sensor of a voltage-gated mammalian potassium channel.

1993 ◽  
Vol 268 (32) ◽  
pp. 23777-23779
Author(s):  
J Tytgat ◽  
K Nakazawa ◽  
A Gross ◽  
P Hess
Keyword(s):  
Potassium Channel ◽  
Voltage Sensor ◽  
Voltage Gated

scholarly journals The trajectory of discrete gating charges in a voltage-gated potassium channel

2020 ◽  
Author(s):  
Michael F. Priest ◽  
Elizabeth E.L. Lee ◽  
Francisco Bezanilla
Keyword(s):  
Potassium Channel ◽  
Voltage Sensor ◽  
Drive Voltage ◽  
Shaker Potassium Channel ◽  
Voltage Gated ◽  
Charged Amino Acids ◽  
Voltage Gated Ion Channels ◽  
Sensing Membrane ◽  
Positively Charged ◽  
Gating Charges

AbstractPositively-charged amino acids respond to membrane potential changes to drive voltage sensor movement in voltage-gated ion channels, but determining the trajectory of voltage sensor gating charges has proven difficult. We optically tracked the movement of the two most extracellular charged residues (R1, R2) in the Shaker potassium channel voltage sensor using a fluorescent positively-charged bimane derivative (qBBr) that is strongly quenched by tryptophan. By individually mutating residues to tryptophan within the putative trajectory of gating charges, we observed that the charge pathway during activation is a rotation and a tilted translation that differs between R1 and R2 and is distinct from their deactivation pathway. Tryptophan-induced quenching of qBBr also indicates that a crucial residue of the hydrophobic plug is linked to the Cole-Moore shift through its interaction with R1. Finally, we show that this approach extends to additional voltage-sensing membrane proteins using the Ciona intestinalis voltage sensitive phosphatase (CiVSP).

scholarly journals Tracking the movement of discrete gating charges in a voltage-gated potassium channel

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Michael F Priest ◽  
Elizabeth EL Lee ◽  
Francisco Bezanilla
Keyword(s):  
Potassium Channel ◽  
Voltage Sensor ◽  
Charge Motion ◽  
Shaker Potassium Channel ◽  
Voltage Gated ◽  
Charged Amino Acids ◽  
Voltage Gated Ion Channels ◽  
Sensing Membrane ◽  
Positively Charged ◽  
Gating Charges

Positively-charged amino acids respond to membrane potential changes to drive voltage sensor movement in voltage-gated ion channels, but determining the displacements of voltage sensor gating charges has proven difficult. We optically tracked the movement of the two most extracellular charged residues (R1, R2) in the Shaker potassium channel voltage sensor using a fluorescent positively-charged bimane derivative (qBBr) that is strongly quenched by tryptophan. By individually mutating residues to tryptophan within the putative pathway of gating charges, we observed that the charge motion during activation is a rotation and a tilted translation that differs between R1 and R2. Tryptophan-induced quenching of qBBr also indicates that a crucial residue of the hydrophobic plug is linked to the Cole-Moore shift through its interaction with R1. Finally, we show that this approach extends to additional voltage-sensing membrane proteins using the Ciona intestinalis voltage sensitive phosphatase (CiVSP) (Murata et al., 2005a).

scholarly journals Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Keenan C Taylor ◽  
Po Wei Kang ◽  
Panpan Hou ◽  
Nien-Du Yang ◽  
Georg Kuenze ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Intermediate State ◽  
Three Dimensional ◽  
Voltage Sensor ◽  
Dimensional Structure ◽  
Delayed Rectifier ◽  
Voltage Gated ◽  
Delayed Rectifier Current ◽  
Activated State ◽  
Voltage Gated Ion Channels

Voltage-gated ion channels feature voltage sensor domains (VSDs) that exist in three distinct conformations during activation: resting, intermediate, and activated. Experimental determination of the structure of a potassium channel VSD in the intermediate state has previously proven elusive. Here, we report and validate the experimental three-dimensional structure of the human KCNQ1 voltage-gated potassium channel VSD in the intermediate state. We also used mutagenesis and electrophysiology in Xenopus laevisoocytes to functionally map the determinants of S4 helix motion during voltage-dependent transition from the intermediate to the activated state. Finally, the physiological relevance of the intermediate state KCNQ1 conductance is demonstrated using voltage-clamp fluorometry. This work illuminates the structure of the VSD intermediate state and demonstrates that intermediate state conductivity contributes to the unusual versatility of KCNQ1, which can function either as the slow delayed rectifier current (IKs) of the cardiac action potential or as a constitutively active epithelial leak current.

scholarly journals Computer simulation of the KvAP voltage-gated potassium channel: steered molecular dynamics of the voltage sensor

FEBS Letters ◽  
2004 ◽  
Vol 564 (3) ◽  
pp. 325-332 ◽  
Author(s):  
Luca Monticelli ◽  
Kindal M. Robertson ◽  
Justin L. MacCallum ◽  
D.Peter Tieleman
Keyword(s):  
Molecular Dynamics ◽  
Computer Simulation ◽  
Potassium Channel ◽  
Steered Molecular Dynamics ◽  
Voltage Sensor ◽  
Voltage Gated

scholarly journals Position and motions of the S4 helix during opening of the Shaker potassium channel

2010 ◽  
Vol 136 (6) ◽  
pp. 629-644 ◽  
Author(s):  
L. Revell Phillips ◽  
Kenton J. Swartz
Keyword(s):  
Potassium Channel ◽  
Open Channels ◽  
Shaker Potassium Channel ◽  
Voltage Sensors ◽  
Voltage Gated ◽  
Kv Channels ◽  
Close Proximity ◽  
Pore Domain ◽  
Significant Distance ◽  
Average Position

The four voltage sensors in voltage-gated potassium (Kv) channels activate upon membrane depolarization and open the pore. The location and motion of the voltage-sensing S4 helix during the early activation steps and the final opening transition are unresolved. We studied Zn2+ bridges between two introduced His residues in Shaker Kv channels: one in the R1 position at the outer end of the S4 helix (R362H), and another in the S5 helix of the pore domain (A419H or F416H). Zn2+ bridges readily form between R362H and A419H in open channels after the S4 helix has undergone its final motion. In contrast, a distinct bridge forms between R362H and F416H after early S4 activation, but before the final S4 motion. Both bridges form rapidly, providing constraints on the average position of S4 relative to the pore. These results demonstrate that the outer ends of S4 and S5 remain in close proximity during the final opening transition, with the S4 helix translating a significant distance normal to the membrane plane.

scholarly journals Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors

2018 ◽  
Vol 150 (8) ◽  
pp. 1215-1230 ◽  
Author(s):  
Sara I. Liin ◽  
Per-Eric Lund ◽  
Johan E. Larsson ◽  
Johan Brask ◽  
Björn Wallner ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Action Potential ◽  
Ion Channel ◽  
Potassium Channel ◽  
Voltage Sensor ◽  
Pharmaceutical Drugs ◽  
Voltage Gated ◽  
Channel Opening ◽  
Ion Conducting ◽  
Voltage Gated Ion Channels

Voltage-gated ion channels are key molecules for the generation of cellular electrical excitability. Many pharmaceutical drugs target these channels by blocking their ion-conducting pore, but in many cases, channel-opening compounds would be more beneficial. Here, to search for new channel-opening compounds, we screen 18,000 compounds with high-throughput patch-clamp technology and find several potassium-channel openers that share a distinct biaryl-sulfonamide motif. Our data suggest that the negatively charged variants of these compounds bind to the top of the voltage-sensor domain, between transmembrane segments 3 and 4, to open the channel. Although we show here that biaryl-sulfonamide compounds open a potassium channel, they have also been reported to block sodium and calcium channels. However, because they inactivate voltage-gated sodium channels by promoting activation of one voltage sensor, we suggest that, despite different effects on the channel gates, the biaryl-sulfonamide motif is a general ion-channel activator motif. Because these compounds block action potential–generating sodium and calcium channels and open an action potential–dampening potassium channel, they should have a high propensity to reduce excitability. This opens up the possibility to build new excitability-reducing pharmaceutical drugs from the biaryl-sulfonamide scaffold.

scholarly journals Atomic Constraints between the Voltage Sensor and the Pore Domain in a Voltage-gated K+ Channel of Known Structure

2008 ◽  
Vol 131 (6) ◽  
pp. 549-561 ◽  
Author(s):  
Anthony Lewis ◽  
Vishwanath Jogini ◽  
Lydia Blachowicz ◽  
Muriel Lainé ◽  
Benoît Roux
Keyword(s):  
Structural Model ◽  
Voltage Sensor ◽  
K Channel ◽  
Structural Reorganization ◽  
Voltage Gated ◽  
Transmembrane Segments ◽  
Close Physical Proximity ◽  
Activated State ◽  
Dynamics Simulations ◽  
Pore Domain

In voltage-gated K+ channels (Kv), membrane depolarization promotes a structural reorganization of each of the four voltage sensor domains surrounding the conducting pore, inducing its opening. Although the crystal structure of Kv1.2 provided the first atomic resolution view of a eukaryotic Kv channel, several components of the voltage sensors remain poorly resolved. In particular, the position and orientation of the charged arginine side chains in the S4 transmembrane segments remain controversial. Here we investigate the proximity of S4 and the pore domain in functional Kv1.2 channels in a native membrane environment using electrophysiological analysis of intersubunit histidine metallic bridges formed between the first arginine of S4 (R294) and residues A351 or D352 of the pore domain. We show that histidine pairs are able to bind Zn2+ or Cd2+ with high affinity, demonstrating their close physical proximity. The results of molecular dynamics simulations, consistent with electrophysiological data, indicate that the position of the S4 helix in the functional open-activated state could be shifted by ∼7–8 Å and rotated counterclockwise by 37° along its main axis relative to its position observed in the Kv1.2 x-ray structure. A structural model is provided for this conformation. The results further highlight the dynamic and flexible nature of the voltage sensor.

scholarly journals Molecular Movement of the Voltage Sensor in a K Channel

2003 ◽  
Vol 122 (6) ◽  
pp. 741-748 ◽  
Author(s):  
Amir Broomand ◽  
Roope Männikkö ◽  
H. Peter Larsson ◽  
Fredrik Elinder
Keyword(s):  
Voltage Sensor ◽  
Disulphide Bond ◽  
K Channel ◽  
Crystallographic Structure ◽  
X Ray ◽  
Voltage Gated ◽  
Disulphide Bonds ◽  
State Dependent ◽  
Molecular Movement ◽  
Pore Domain

The X-ray crystallographic structure of KvAP, a voltage-gated bacterial K channel, was recently published. However, the position and the molecular movement of the voltage sensor, S4, are still controversial. For example, in the crystallographic structure, S4 is located far away (>30 Å) from the pore domain, whereas electrostatic experiments have suggested that S4 is located close (<8 Å) to the pore domain in open channels. To test the proposed location and motion of S4 relative to the pore domain, we induced disulphide bonds between pairs of introduced cysteines: one in S4 and one in the pore domain. Several residues in S4 formed a state-dependent disulphide bond with a residue in the pore domain. Our data suggest that S4 is located close to the pore domain in a neighboring subunit. Our data also place constraints on possible models for S4 movement and are not compatible with a recently proposed KvAP model.

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