MUTATIONS AFFECTING INTERNAL TEA BLOCKADE IDENTIFY THE PROBABLE PORE-FORMING REGION OF A K+ CHANNEL
MUTATIONS AFFECTING INTERNAL TEA BLOCKADE IDENTIFY THE PROBABLE PORE-FORMING REGION OF A K+ CHANNEL
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DOI：
10.1126/science.2000494
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发表时间：
1991-02-22
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：
YELLEN, G;JURMAN, ME;MACKINNON, R
电压激活钾通道的活性部位是一个跨膜水孔，允许离子以快速但高度选择性的方式渗透细胞膜。 钾选择性通道孔的有用探针是有机离子四乙基铵（TEA），其以毫摩尔亲和力结合到孔的细胞内开口并阻断钾电流。 在由果蝇Shaker基因编码的钾通道中，现在已经通过定点诱变鉴定了特异性影响细胞内TEA亲和力的氨基酸残基。 该残基位于18个氨基酸的保守延伸的中间，该保守延伸将两个位置分开，这两个位置都靠近孔的外部开口。 这些发现表明，这个保守的区域是密切参与的电压激活钾通道的离子传导孔的形成。 此外，只有8个氨基酸残基的一段必须穿过80%的跨膜电位差。
The active site of voltage-activated potassium channels is a transmembrane aqueous pore that permits ions to permeate the cell membrane in a rapid yet highly selective manner. A useful probe for the pore of potassium-selective channels is the organic ion tetraethylammonium (TEA), which binds with millimolar affinity to the intracellular opening of the pore and blocks potassium current. In the potassium channel encoded by the Drosophila Shaker gene, an amino acid residue that specifically affects the affinity for intracellular TEA has now been identified by site-directed mutagenesis. This residue is in the middle of a conserved stretch of 18 amino acids that separates two locations that are both near the external opening of the pore. These findings suggest that this conserved region is intimately involved in the formation of the ion conduction pore of voltage-activated potassium channels. Further, a stretch of only eight amino acid residues must traverse 80 percent of the transmembrane electric potential difference.