SIB Swiss Institute of Bioinformatics, University of Basel, Basel, Switzerland.
Biozentrum, University of Basel, Basel, Switzerland.
Elife. 2017 Oct 10;6:e25844. doi: 10.7554/eLife.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.
钾通道可被配体和/或膜电位开启。在电压门控钾通道和原核的 KcsA 通道中，导通被认为是由于阻止离子进入孔道的细胞内缩窄的打开而产生的。另一方面，许多配体门控钾通道缺乏这样的门，这表明它们可能通过孔道外侧面的选择性过滤器（狭窄区域）内的变化而被激活。通过分子动力学模拟和电生理学测量，我们表明，配体诱导的 KcsA 通道构象变化消除了选择性过滤器处的空间位阻，从而导致结构波动、钾亲和力降低和离子渗透性增加。这种选择性过滤器的激活可能是 K 通道中普遍的门控机制。在细胞内门水平上的孔道阻塞似乎是次要的。
