A single ring of charged amino acids at one end of the pore can control ion selectivity in the 5-HT3 receptor
A single ring of charged amino acids at one end of the pore can control ion selectivity in the 5-HT3 receptor
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DOI：
10.1038/sj.bjp.0705424
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发表时间：
2003-09-01
影响因子：
7.3
通讯作者：
Lummis, SCR
中科院分区：
文献类型：
--
作者：
Thompson, AJ;Lummis, SCR
为了确定阳离子或阴离子特异性通道在这些离子之间选择的机制，我们研究了静电因子在典型的配体门控离子通道，5-羟色胺（3）（5-HT 3）受体中的作用，通过去除和/或插入孔两端的保守带电残基环。2中和通道细胞内端的负电荷环（E-1 'A）导致非选择性通道（P-Na/P-Cl=0.89）。3在孔的细胞外末端插入带正电荷的残基，要么产生无功能的受体（A24 ′ K），要么产生保持阳离子选择性的受体。（P-Na/P-Cl=110; S19 'R）。4然而，将带负电荷的环（E-1' A）的去除与带正电荷的环（S19 'R）的插入相结合，导致主要是阴离子选择性的通道（P-Na/P-Cl=0.37）。5数据表明，对于阳离子选择性5-HT 3受体，由孔两端的带电环施加的选择性控制由通道细胞内侧的带负电荷残基的环支配。由于改变该位置的电荷也已显示改变阴离子选择性受体中的离子选择性，因此这些数据表明静电因素可以控制整个Cys环家族中的选择性。
1 To determine the mechanisms by which cation- or anion-specific channels select between these ions, we have examined the role of electrostatic factors in a typical ligand-gated ion channel, the 5-hydroxytryptamine(3) (5-HT3) receptor, by removal and/or insertion of rings of conserved charged residues at either end of the pore.2 Neutralization of the negatively charged ring at the intracellular end of the channel (E-1'A) results in a nonselective channel (P-Na/P-Cl=0.89).3 Insertion of positively charged residues at the extracellular end of the pore either results in a nonfunctional receptor (A24'K) or one that remains cation- selective (P-Na/P-Cl=110; S19'R).4 Combining the removal of a negatively charged ring (E-1'A) with the insertion of a positively charged ring (S19'R), however, results in a channel that is predominantly anion-selective (P-Na/P-Cl=0.37).5 The data suggest that for the cation- selective 5-HT3 receptor, the control of selectivity exerted by charged rings at either end of the pore is dominated by the ring of negatively charged residues at the intracellular side of the channel. As changing the charge at this position has also been shown to change ionic selectivity in anion-selective receptors, these data suggest that electrostatic factors can control selectivity in the whole Cys-loop family.