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

• Main Authors: Florian T Heer, David J Posson, Wojciech Wojtas-Niziurski, Crina M Nimigean, Simon Bernèche
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2017-10-01
• Series: eLife
• Subjects: ion channel; conductance; gating; pH gated; allostery; molecular dynamics
• Online Access: https://elifesciences.org/articles/25844

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.