调整离子配位偏好以实现选择性渗透
Tuning ion coordination preferences to enable selective permeation
摘要：
钾（K-）通道催化K+离子渗透穿过细胞膜，同时将它们的渗透区分为Na+离子的一千倍以上。结构研究表明，裸露的K+离子占据的最西部的通道区域在一个高度协调的状态下，所有8个周围的氧配体从通道壁。与大多数通道一样，当一种离子与水相比优先被通道稳定或不稳定时，选择性的驱动力就会出现。在通常的机制观点中，通过教科书图形生动地显示，K-通道中选择性的驱动力是由拟合产生的，由此通道通过在能量和局部结构方面为K+提供类似水的环境来诱导K+离子离开水。在液体环境中的局部离子配位的知识转化为蛋白质离子通道中的设计参数，产生类似的能量稳定性的含义，已经没有受到挑战，可能部分是由于缺乏共识，在液态水中的离子配位结构。然而，越来越多的证据表明，在液态水中配位K+离子的配位体数量较少，排列方式不同，这就提出了有关机制的新问题：离子配位偏好如何以及为什么会改变，以及这如何改变目前的离子选择性概念？我们的研究为K+离子通道选择性机制提供了一个新的通道中心范式。因为通道环境不是液体状的，所以通道必然引起离子配位偏好的局部结构变化，这使得离子之间能够进行结构和能量区分。
英文摘要：
Potassium (K-) channels catalyze K+ ion permeation across cellular membranes while simultaneously discriminating their permeation over Na+ ions by more than a factor of a thousand. Structural studies show bare K+ ions occupying the narrowest channel regions in a state of high coordination by all 8 surrounding oxygen ligands from the channel walls. As in most channels, the driving force for selectivity occurs when one ion is preferentially stabilized or destabilized by the channel compared to water. In the common view of mechanism, made vivid by textbook graphics, the driving force for selectivity in K- channels arises by a fit, whereby the channel induces K+ ions to leave water by offering an environment like water for K+, in terms of both energy and local structure. The implication that knowledge of local ion coordination in a liquid environment translates to design parameters in a protein ion channel, producing similar energetic stabilities, has gone unchallenged, presumably due in part to lack of consensus regarding ion coordination structures in liquid water. Growing evidence that smaller numbers and different arrangements of ligands coordinate K+ ions in liquid water, however, raises new questions regarding mechanism: how and why should ion coordination preferences change, and how does that alter the current notions of ion selectivity? Our studies lead to a new channelcentric paradigm for the mechanism of K+ ion channel selectivity. Because the channel environment is not liquid-like, the channel necessarily induces local structural changes in ion coordination preferences that enable structural and energetic differentiation between ions.
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