Molecular basis of ion permeability in a voltage-gated sodium channel.
Molecular basis of ion permeability in a voltage-gated sodium channel.
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DOI：
10.15252/embj.201593285
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发表时间：
2016-04-15
期刊：
影响因子：
--
通讯作者：
Wallace BA
中科院分区：
文献类型：
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作者：
Naylor CE;Bagnéris C;DeCaen PG;Sula A;Scaglione A;Clapham DE;Wallace BA
电压门控钠通道对于跨细胞膜的电信号传导至关重要。与其他阳离子相比，它们对钠离子表现出很强的选择性，从而能够精细调节与动作电位相关的级联事件。该论文描述了原核钠通道的离子渗透特性和晶体结构，首次展示了钠离子在钠通道选择性过滤器中的详细位置。基于结构的静电计算与针对这些通道测量的相对阳离子渗透率比率（Na+≈Li+≫K+、Ca2+、Mg2+）一致。在构建为改变离子选择性的 E178D 选择性过滤器突变体中，最靠近细胞外侧的钠离子结合位点缺失。与钾通道中的钾离子不同，这些通道中的钠离子似乎是水合的，并且与选择性过滤器残留物的侧链相关，而不是与多肽主链相关。
Voltage‐gated sodium channels are essential for electrical signalling across cell membranes. They exhibit strong selectivities for sodium ions over other cations, enabling the finely tuned cascade of events associated with action potentials. This paper describes the ion permeability characteristics and the crystal structure of a prokaryotic sodium channel, showing for the first time the detailed locations of sodium ions in the selectivity filter of a sodium channel. Electrostatic calculations based on the structure are consistent with the relative cation permeability ratios (Na+ ≈ Li+ ≫ K+, Ca2+, Mg2+) measured for these channels. In an E178D selectivity filter mutant constructed to have altered ion selectivities, the sodium ion binding site nearest the extracellular side is missing. Unlike potassium ions in potassium channels, the sodium ions in these channels appear to be hydrated and are associated with side chains of the selectivity filter residues, rather than polypeptide backbones.