CONTROL OF RECTIFICATION AND PERMEATION BY RESIDUES IN 2 DISTINCT DOMAINS IN AN INWARD RECTIFIER K+ CHANNEL
CONTROL OF RECTIFICATION AND PERMEATION BY RESIDUES IN 2 DISTINCT DOMAINS IN AN INWARD RECTIFIER K+ CHANNEL
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DOI：
10.1016/0896-6273(95)90343-7
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发表时间：
1995-05-01
期刊：
影响因子：
16.2
通讯作者：
JAN, LY
中科院分区：
文献类型：
--
作者：
YANG, J;JAN, YN;JAN, LY
内向整流钾通道比外向电流向内传导更多，这是由于细胞内镁离子和多胺对通道孔的电压依赖性阻断所致。我们研究了强整流通道IRK1中内向整流和离子渗透的分子机制和结构决定因素。发现镁离子和多胺的封闭不符合一对一的结合，这表明一个通道孔可以容纳不止一个封闭粒子。亲水性C-末端结构域中的一个带负电荷的氨基酸被发现对内向整流和离子渗透都是关键的。该残基和可能的第二跨膜片段(M2)上的负电荷残基独立地促进了镁与多胺的高亲和力结合。该残基的突变还诱导不依赖于镁离子和多胺的内向整流，并显著改变单通道行为。我们认为，亲水性C-末端结构域构成了通道孔的一部分，而亲水性和疏水性结构域在孔壁的参与可能为内向整流K+通道的多离子、长孔性质提供了分子基础。
Inwardly rectifying K+ channels conduct more inward than outward current as a result of voltage-dependent block of the channel pore by intracellular Mg2+ and polyamines. We investigated the molecular mechanism and structural determinants of inward rectification and ion permeation in a strongly rectifying channel, IRK1. Block by Mg2+ and polyamines is found not to conform to one-to-one binding, suggesting that a channel pore can accommodate more than one blocking particle. A negatively charged amino acid in the hydrophilic C-terminal domain is found to be critical for both inward rectification and ion permeation. This residue and a negatively charged residue in the putative second transmembrane segment (M2) contribute independently to high affinity binding of Mg2+ and polyamines. Mutation of this residue also induces Mg2+- and polyamine-independent inward rectification and dramatically alters single-channel behavior. We propose that the hydrophilic C-terminal domain comprises part of the channel pore and that involvement of both hydrophilic and hydrophobic domains in pore lining may provide a molecular basis for the multi-ion, long-pore nature of inwardly rectifying K+ channels.