TY - JOUR TI - Mechanism of activation at the selectivity filter of the KcsA K+ channel AU - Heer, Florian T AU - Posson, David J AU - Wojtas-Niziurski, Wojciech AU - Nimigean, Crina M AU - Bernèche, Simon A2 - Swartz, Kenton J VL - 6 PY - 2017 DA - 2017/10/10 SP - e25844 C1 - eLife 2017;6:e25844 DO - 10.7554/eLife.25844 UR - https://doi.org/10.7554/eLife.25844 AB - 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. KW - ion channel KW - conductance KW - gating KW - pH gated KW - allostery KW - molecular dynamics KW - free energy calculations JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -