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Mechanism of activation at the selectivity filter of the KcsA K+ channel.

ABSTRACT: Potassium channels are opened by ligands and/or membrane potential. In voltage-gated K+ channels and the prokaryotic KcsA channel, conduction is believed to result from opening of an intracellular constriction that prevents ion entry into the pore. On the other hand, numerous ligand-gated K+ channels lack such gate, suggesting that they may be activated by a change within the selectivity filter, a narrow region at the extracellular side of the pore. Using molecular dynamics simulations and electrophysiology measurements, we show that ligand-induced conformational changes in the KcsA channel removes steric restraints at the selectivity filter, thus resulting in structural fluctuations, reduced K+ affinity, and increased ion permeation. Such activation of the selectivity filter may be a universal gating mechanism within K+ channels. The occlusion of the pore at the level of the intracellular gate appears to be secondary.

SUBMITTER: Heer FT

PROVIDER: S-EPMC5669632 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Mechanism of activation at the selectivity filter of the KcsA K+ channel.

Heer Florian T FT Posson David J DJ Wojtas-Niziurski Wojciech W Nimigean Crina M CM Bernèche Simon S

eLife 20171010

Potassium channels are opened by ligands and/or membrane potential. In voltage-gated K+ channels and the prokaryotic KcsA channel, conduction is believed to result from opening of an intracellular constriction that prevents ion entry into the pore. On the other hand, numerous ligand-gated K+ channels lack such gate, suggesting that they may be activated by a change within the selectivity filter, a narrow region at the extracellular side of the pore. Using molecular dynamics ...[more]

PMID: 28994652

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