Gating-associated clustering-dispersion dynamics of the KcsA potassium channel in a lipid membrane
Gating-associated clustering-dispersion dynamics of the KcsA potassium channel in a lipid membrane
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脂膜中 KcsA 钾通道的门控相关聚类分散动力学
DOI：
10.1021/jz402491t
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发表时间：
2014
影响因子：
4.4
通讯作者：
S. Oiki
中科院分区：
文献类型：
--
作者：
A. Sumino;D. Yamamoto;M. Iwamoto;T. Dewa;S. Oiki
KcsA钾通道是细菌来源的典型通道，其pH依赖性门控机制已被广泛研究。利用高分辨率原子力显微镜（AFM），我们分辨了KcsA通道在膜包埋条件下的功能性开、关门。在这里，我们惊讶地发现，pH依赖性门控的KcsA通道与集群分散动力学。在中性pH下，静止的封闭通道聚结，形成纳米簇。在酸性pH下，开放门控通道分散为单个孤立的通道。延时AFM揭示了可逆的集群分散过渡pH值的变化。在酸性平衡下，一小部分通道是纳米簇，其中门显然是关闭的。因此，有人建议，开放的门和分散是紧密相连的。分子内构象变化和超分子聚集-分散动力学之间的相互作用为理解前所未有的通道功能协同性提供了见解。
The KcsA potassium channel is a prototypical channel of bacterial origin, and the mechanism underlying the pH-dependent gating has been studied extensively. With the high-resolution atomic force microscopy (AFM), we have resolved functional open and closed gates of the KcsA channel under the membrane-embedded condition. Here we surprisingly found that the pH-dependent gating of the KcsA channels was associated with clustering–dispersion dynamics. At neutral pH, the resting, closed channels were coalesced, forming nanoclusters. At acidic pH, the open-gated channels were dispersed as singly isolated channels. Time-lapse AFM revealed reversible clustering–dispersion transitions upon pH changes. At acidic equilibrium, a small fraction of the channels was nanoclustered, in which the gate was apparently closed. Thus, it is suggested that opening of the gate and the dispersion are tightly linked. The interplay between the intramolecular conformational change and the supramolecular clustering–dispersion dynamics provides insights into understanding of unprecedented functional cooperativity of channels.