Stabilization of ion selectivity filter by pore loop ion pairs in an inwardly rectifying potassium channel
Stabilization of ion selectivity filter by pore loop ion pairs in an inwardly rectifying potassium channel
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DOI：
10.1073/pnas.94.4.1568
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发表时间：
1997-02-18
影响因子：
11.1
通讯作者：
Jan, LY
中科院分区：
文献类型：
--
作者：
Yang, J;Yu, M;Jan, LY
离子选择性对于电压依赖的阳离子通道的生物学功能是关键的，并且是通过特定的离子结合到称为选择性过滤器的孔区来实现的，在电压门控K+、Na+和Ca~(2+)通道中，选择性过滤器是由形成通道的四个亚基或内部同源结构域中的每一个提供的位于第五和第六跨膜片段之间的短多肽环(称为H5或P区)形成的，而对电压门控K+通道的诱变研究已经开始揭示该孔区的结构组织，关于维持选择性过滤器结构稳定性的物理和化学相互作用知之甚少，如果我们证明在一个内向整流K+(IRK)通道IRK1中，H5孔环中离子对的短程相互作用对孔结构和离子渗透是至关重要的，两个残基，一个谷氨酸和一个精氨酸，似乎在四聚体通道中形成暴露的盐桥，这种离子对相互作用的改变或破坏显著改变了离子的选择性和渗透性。由于这种离子对在所有的IRK通道中都是保守的，它可能构成了这个通道超家族中维持孔结构稳定的一般机制。
Ion selectivity is critical for the biological functions of voltage-dependent cation channels and is achieved by specific ion binding to a pore region called the selectivity filter, In voltage-gated K+, Na+ and Ca2+ channels, the selectivity filter is formed by a short polypeptide loop (called the H5 or P region) between the fifth and sixth transmembrane segments, donated by each of the four subunits or internal homologous domains forming the channel, While mutagenesis studies on voltage-gated K+ channels have begun to shed light on the structural organization of this pore region, little is known about the physical and chemical interactions that maintain the structural stability of the selectivity filter, Were we show that in an inwardly rectifying K+ (IRK) channel, IRK1, short range interactions of an ion pair in the H5 pore loop are crucial for pore structure and ion permeation, The two residues, a glutamate and an arginine, appear to form exposed salt bridges in the tetrameric channel, Alteration or disruption of such ion pair interactions dramatically alters ion selectivity and permeation. Since this ion pair is conserved in all IRK channels, it may constitute a general mechanism for maintaining the stability of the pore structure in this channel superfamily.