RINGS OF ANIONIC AMINO-ACIDS AS STRUCTURAL DETERMINANTS OF ION SELECTIVITY IN THE ACETYLCHOLINE-RECEPTOR CHANNEL
RINGS OF ANIONIC AMINO-ACIDS AS STRUCTURAL DETERMINANTS OF ION SELECTIVITY IN THE ACETYLCHOLINE-RECEPTOR CHANNEL
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DOI：
10.1098/rspb.1991.0053
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发表时间：
1991-05-22
影响因子：
4.7
通讯作者：
SAKMANN, B
中科院分区：
文献类型：
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作者：
KONNO, T;BUSCH, C;SAKMANN, B
为了深入了解烟碱乙酰胆碱受体（AChR）通道的碱金属阳离子之间的微弱但显着的选择性的分子基础，我们已经确定了单通道电导率和渗透率比的碱金属阳离子特异性突变电鳐在非洲爪蟾卵母细胞中表达的AChR通道。这些突变涉及三个阴离子环（细胞外环、中间环和细胞质环）中的带电和极性侧链，此前已发现这些环决定了通过AChR通道的K+转运速率。所获得的结果表明，在中间环的突变比在细胞外和细胞质环的突变对离子选择性产生更强的影响。实验结果，连同模拟的通道的能量分布，表明形成中间环的氨基酸残基与渗透阳离子紧密接触，并可能代表部分的物理相关的假定的选择性过滤器中的乙酰胆碱受体通道。
To gain an insight into the molecular basis of the weak but significant selectivity among alkali metal cations of the nicotinic acetylcholine receptor (AChR) channel, we have determined single-channel conductance and permeability ratios for alkali metal cations on specifically mutated Torpedo californica AChR channels expressed in Xenopus oocytes. The mutations involved charged and polar side chains in the three anionic rings (extracellular, intermediate and cytoplasmic ring) which have previously been found to determine the rate of K+ transport through the AChR channel. The results obtained reveal that mutations in the intermediate ring exert much stronger effects on ion selectivity than do mutations in the extracellular and the cytoplasmic ring. The experimental results, together with simulations of the channel's energy profile, suggest that the amino acid residues forming the intermediate ring come into close contact with permeating cations and possibly represent part of the physical correlate of the postulated selectivity filter in the AChR channel.