Dataset Information

Catalysis of Na+ permeation in the bacterial sodium channel Na(V)Ab.

ABSTRACT: Determination of a high-resolution 3D structure of voltage-gated sodium channel Na(V)Ab opens the way to elucidating the mechanism of ion conductance and selectivity. To examine permeation of Na(+) through the selectivity filter of the channel, we performed large-scale molecular dynamics simulations of Na(V)Ab in an explicit, hydrated lipid bilayer at 0 mV in 150 mM NaCl, for a total simulation time of 21.6 ?s. Although the cytoplasmic end of the pore is closed, reversible influx and efflux of Na(+) through the selectivity filter occurred spontaneously during simulations, leading to equilibrium movement of Na(+) between the extracellular medium and the central cavity of the channel. Analysis of Na(+) dynamics reveals a knock-on mechanism of ion permeation characterized by alternating occupancy of the channel by 2 and 3 Na(+) ions, with a computed rate of translocation of (6 ± 1) × 10(6) ions?s(-1) that is consistent with expectations from electrophysiological studies. The binding of Na(+) is intimately coupled to conformational isomerization of the four E177 side chains lining the extracellular end of the selectivity filter. The reciprocal coordination of variable numbers of Na(+) ions and carboxylate groups leads to their condensation into ionic clusters of variable charge and spatial arrangement. Structural fluctuations of these ionic clusters result in a myriad of ion binding modes and foster a highly degenerate, liquid-like energy landscape propitious to Na(+) diffusion. By stabilizing multiple ionic occupancy states while helping Na(+) ions diffuse within the selectivity filter, the conformational flexibility of E177 side chains underpins the knock-on mechanism of Na(+) permeation.

SUBMITTER: Chakrabarti N

PROVIDER: S-EPMC3710854 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Catalysis of Na+ permeation in the bacterial sodium channel Na(V)Ab.

Chakrabarti Nilmadhab N Ing Christopher C Payandeh Jian J Zheng Ning N Catterall William A WA Pomès Régis R

Proceedings of the National Academy of Sciences of the United States of America 20130626 28

Determination of a high-resolution 3D structure of voltage-gated sodium channel Na(V)Ab opens the way to elucidating the mechanism of ion conductance and selectivity. To examine permeation of Na(+) through the selectivity filter of the channel, we performed large-scale molecular dynamics simulations of Na(V)Ab in an explicit, hydrated lipid bilayer at 0 mV in 150 mM NaCl, for a total simulation time of 21.6 μs. Although the cytoplasmic end of the pore is closed, reversible influx and efflux of N ...[more]

PMID: 23803856

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Dataset Information

Catalysis of Na+ permeation in the bacterial sodium channel Na(V)Ab.

Publications

Catalysis of Na+ permeation in the bacterial sodium channel Na(V)Ab.

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