ROLE OF H5 DOMAIN IN DETERMINING PORE DIAMETER AND ION PERMEATION THROUGH CYCLIC NUCLEOTIDE-GATED CHANNELS
ROLE OF H5 DOMAIN IN DETERMINING PORE DIAMETER AND ION PERMEATION THROUGH CYCLIC NUCLEOTIDE-GATED CHANNELS
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DOI：
10.1038/364061a0
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发表时间：
1993-07-01
期刊：
影响因子：
64.8
通讯作者：
SIEGELBAUM, SA
中科院分区：
文献类型：
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作者：
GOULDING, EH;TIBBS, GR;SIEGELBAUM, SA
离子通过膜通道的渗透被认为是由一个狭窄的区域的通道孔称为选择性过滤器1，这已被提出来区分离子之间的特异性结合和分子筛，由孔径确定。最近的证据表明，电压门控钾离子通道2 -8、钠离子通道9 -13和钙离子通道12中的保守结构域（称为H5、P或SS 1-SS 2）有助于孔的内衬。在这里，我们调查是否H5域决定孔径和检查孔径在控制离子渗透的作用。这些研究依赖于从牛视网膜14和鲶鱼嗅觉神经元15克隆的环核苷酸门控通道之间的单通道电导、离子选择性和表观孔径的差异。使用嵌合视网膜嗅觉通道，我们发现H5结构域决定了渗透特性的这些差异，提供了环核苷酸门控通道确实是电压门控通道家族成员的结构证据15 -17。此外，这些结果直接表明H5结构域有助于形成选择性过滤器，并且分子筛在控制离子渗透中是重要的。
ION permeation through membrane channels is thought to be governed by a narrow region of the channel pore termed the selectivity filter1, which has been proposed to discriminate among ions by both specific binding and molecular sieving, as determined by pore diameter. Recent evidence suggests that a conserved domain (known as H5, P or SS1-SS2) in voltage-gated potassium2-8, sodium9-13 and calcium12channels contributes to the lining of the pore. Here we investigate whether the H5 domain determines pore diameter and examine the role of pore diameter in controlling ion permeation. These studies rely on differences in single channel conductance, ion selectivity and apparent pore diameter between cyclic nucleotide-gated channels cloned from bovine retina14 and catfish olfactory neurons15. Using chimaeric retinal-olfactory channels, we find that the H5 domain determines these differences in permeation properties, providing structural evidence that the cyclic nucleotide-gated channels are indeed members of the voltage-gated channel family15-17. Moreover, these results show directly that the H5 domain helps form the selectivity filter and that molecular sieving is important in controlling ion permeation.