A FUNCTIONAL CONNECTION BETWEEN THE PORES OF DISTANTLY RELATED ION CHANNELS AS REVEALED BY MUTANT K+ CHANNELS
A FUNCTIONAL CONNECTION BETWEEN THE PORES OF DISTANTLY RELATED ION CHANNELS AS REVEALED BY MUTANT K+ CHANNELS
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DOI：
10.1126/science.1279807
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发表时间：
1992-11-13
期刊：
影响因子：
56.9
通讯作者：
MACKINNON, R
中科院分区：
文献类型：
--
作者：
HEGINBOTHAM, L;ABRAMSON, T;MACKINNON, R
视网膜和嗅觉神经元的电压激活K+通道和环核苷酸门控离子通道之间的总体序列相似性表明，它们起源于共同的祖先。在序列比较的基础上，突变被引入到电压激活的K+通道的孔中。这些突变赋予了环核苷酸门控离子通道离子传导的基本特征；突变的K+通道在单价阳离子中表现出很小的选择性，并被二价阳离子阻断。K+选择性的性质与两种氨基酸的存在有关，这两种氨基酸不在环核苷酸门控通道的成孔区。这些数据表明，离子通道一级结构上的微小差异可以解释极大的功能多样性，它们表明K+、Ca~(2+)和环核苷酸门控离子通道的成孔区之间可能存在联系。
The overall sequence similarity between the voltage-activated K+ channels and cyclic nucleotide-gated ion channels from retinal and olfactory neurons suggests that they arose from a common ancestor. On the basis of sequence comparisons, mutations were introduced into the pore of a voltage-activated K+ channel. These mutations confer the essential features of ion conduction in the cyclic nucleotide-gated ion channels; the mutant K+ channels display little selectivity among monovalent cations and are blocked by divalent cations. The property of K+ selectivity is related to the presence of two amino acids that are absent from the pore-forming region of the cyclic nucleotide-gated channels. These data demonstrate that very small differences in the primary structure of an ion channel can account for extreme functional diversity, and they suggest a possible connection between the pore-forming regions of K+, Ca2+, and cyclic nucleotide-gated ion channels.