author={Jian Payandeh and Todd Scheuer and Ning Zheng and William A. Catterall},
  pages={353 - 358}
Voltage-gated sodium (NaV) channels initiate electrical signalling in excitable cells and are the molecular targets for drugs and disease mutations, but the structural basis for their voltage-dependent activation, ion selectivity and drug block is unknown. Here we report the crystal structure of a voltage-gated Na+ channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation with four activated voltage sensors at 2.7 Å resolution. The arginine gating charges make multiple… 

Crystal structure of a voltage-gated sodium channel in two potentially inactivated states

Crystallographic snapshots of the wild-type NaVAb channel from Arcobacter butzleri captured in two potentially inactivated states provide new insights intoNaV channel gating and novel avenues to drug development and therapy for a range of debilitating NaV channelopathies.

Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel

The crystal structure of NavRh, a NaChBac orthologue from the marine alphaproteobacterium HIMB114, is reported, and it is proposed that NavRh is in an ‘inactivated’ conformation, which may underlie the electromechanical coupling mechanism of voltage-gated channels.

Structural basis for gating charge movement in the voltage sensor of a sodium channel

High-resolution structural models of resting, intermediate, and activated states of the voltage-sensing domain of the bacterial sodium channel NaChBac are constructed using the Rosetta modeling method, crystal structures of related channels, and experimental data showing state-dependent interactions between the gating charge-carrying arginines in the S4 segment and negatively charged residues in neighboring transmembrane segments.

Comparisons of voltage-gated sodium channel structures with open and closed gates and implications for state-dependent drug design.

Here it is identified for the first time how changes in the fenestrations in the hydrophobic TM region associated with the opening of the intracellular gate could modulate the state-dependent ingress and binding of drugs in the TM cavity, in a way that could be exploited for rational drug design.

Ion conduction and conformational flexibility of a bacterial voltage-gated sodium channel

An almost barrier-less three-ion conduction mechanism involving competing knock-on and “pass-by” processes, intimately linked to signature glutamate ring protonation and structural isomerizations is described.

Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel

Structure of the Cardiac Sodium Channel

Exploring conformational states of the bacterial voltage-gated sodium channel NavAb via molecular dynamics simulations

Gating charge computations suggest that a structural rearrangement comparable to that occurring between activated-open and resting-closed states is required to explain experimental values of the gating charge, thereby confirming that the reported VSD structure is likely an intermediate along the channel activation pathway.



Voltage sensor conformations in the open and closed states in ROSETTA structural models of K(+) channels.

A unified mechanism of voltage-dependent gating for K(v)1.2 and KvAP in which this major conformational change moves the gating charge across the electric field in an analogous way for both channels is proposed.

Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment

The detailed structure of a chimaeric voltage-dependent K+ channel, which the authors call the ‘paddle-chimaera channel’, is described, which explains charge stabilization within the membrane and suggests a mechanism for voltage-sensor movements and pore gating.

The structure of the potassium channel: molecular basis of K+ conduction and selectivity.

The architecture of the pore establishes the physical principles underlying selective K+ conduction, which promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter.

Calcium channel characteristics conferred on the sodium channel by single mutations

The effects on ion selectivity of replacing lysine at position 1,422 in repeat III and/or alanine in repeat IV of rat sodium channel II are reported, suggesting that these residues constitute part of the selectivity filter of the channel.

Two Separate Interfaces between the Voltage Sensor and Pore Are Required for the Function of Voltage-Dependent K+ Channels

The crystal structure and published mutational studies support the hypothesis that the S4-S5 linkers convert voltage-sensor motions directly into gate opening and closing, and it is demonstrated through mutagenesis that this interface is necessary for the function and/or structure of two different Kv channels.

Disulfide locking a sodium channel voltage sensor reveals ion pair formation during activation

Voltage-dependent formation of an ion pair during activation of the voltage sensor is demonstrated in real time and it is suggested that this interaction catalyzes S4 movement and channel activation.

Structural studies of ion permeation and Ca2+ blockage of a bacterial channel mimicking the cyclic nucleotide-gated channel pore

The structural analysis of a set of mimics of CNG channel pores reveals that the conserved acidic residue in the filter is essential for Ca2+ binding but not through direct ion chelation as in the currently accepted view.

Selectivity filter residues contribute unequally to pore stabilization in voltage-gated sodium channels.

Data suggest that an electrostatic interaction between the positively charged residue K1237 and the negatively charged residue D400 stabilizes the structure of the pore and thereby prevents I(US), which appears to provide the basis for selective permeation of Na+ over K+.