K channel gating by an affinity-switching selectivity filter.
K channel gating by an affinity-switching selectivity filter.
复制标题
通过亲和开关选择性滤光片进行 K 通道门控。
DOI：
10.1073/pnas.0308743101
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发表时间：
2004
影响因子：
11.1
通讯作者：
VanDongen,AntoniusMJ
中科院分区：
文献类型：
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作者：
VanDongen,AntoniusMJ
离子通道的普遍性质是它们在两种渗透状态（开放和封闭）之间交替随机的能力。这种行为被认为是由空间“门”控制的，空间“门”是一种在关闭状态下物理上阻碍离子流动并在通道打开期间移动的结构。在theShakerK通道中采用宏观电流的实验表明，该门位于细胞质中。KcsA K通道的晶体结构确实揭示了细胞质收缩，这意味着门和选择性过滤器定位于渗透途径的两端。然而，K通道亚电导行为的分析表明，通道开放（门控）和渗透之间的严格耦合。选择性滤波器是门的想法，因此，通过使用Monte Carlo模拟进行了研究。门控是通过允许过滤器在两种构象之间交替随机选择来实现的：高亲和力状态，其选择性地结合K离子（但不是Na离子）并捕获它们，以及完全非选择性的低亲和力状态，其允许Na和K离子渗透。这些模拟的结果表明，亲和开关不仅赋予选择性过滤器的门控能力，它也允许有效的渗透，而不损害离子的选择性。在这个模型中，渗透和浇口是由同一个过程产生的。
A universal property of ion channels is their ability to alternate stochastically between two permeation states, open and closed. This behavior is thought to be controlled by a steric “gate”, a structure that physically impedes ion flow in the closed state and moves out of the way during channel opening. Experiments employing macroscopic currents in theShakerK channel have suggested a cytoplasmic localization for the gate. Crystallographic structures of the KcsA K channel indeed reveal a cytoplasmic constriction, implying that the gate and selectivity filter are localized to opposite ends of the permeation pathway. However, analysis of K channel subconductance behavior has suggested a strict coupling between channel opening (gating) and permeation. The idea that the selectivity filter is the gate was therefore investigated by using Monte Carlo simulations. Gating is accomplished by allowing the filter to alternate stochastically between two conformations: a high-affinity state, which selectively binds K ions (but not Na ions) and traps them, and a completely nonselective, low-affinity state, which allows both Na and K ions to permeate. The results of these simulations indicate that affinity switching not only endows the selectivity filter with gating abilities, it also allows efficient permeation without jeopardizing ion selectivity. In this model, permeation and gating result from the same process.