MUTANT POTASSIUM CHANNELS WITH ALTERED BINDING OF CHARYBDOTOXIN, A PORE-BLOCKING PEPTIDE INHIBITOR
MUTANT POTASSIUM CHANNELS WITH ALTERED BINDING OF CHARYBDOTOXIN, A PORE-BLOCKING PEPTIDE INHIBITOR
复制标题
DOI：
10.1126/science.2476850
复制
发表时间：
1989-09-22
期刊：
影响因子：
56.9
通讯作者：
MILLER, C
中科院分区：
文献类型：
--
作者：
MACKINNON, R;MILLER, C
研究了胭脂虫毒素对非洲爪蟾卵母细胞中表达的A型钾通道的抑制作用，用于果蝇Shaker基因的几种剪接变体和该通道的几种定点突变体。当用谷氨酰胺取代谷氨酸-422时，Charybdotoxin阻断亲和力降低了3.5倍，当在该位置取代赖氨酸时，降低了约12倍。用天冬氨酸替代谷氨酸-422对毒素亲和力没有影响。因此，在该钾通道的位置422处的谷氨酸残基靠近或在钾传导途径的面向外部的口部中，并且带正电荷的毒素通过由谷氨酸-422建立的负电位静电地集中到其阻断位点。
The inhibition by charybdotoxin of A-type potassium channels expressed in Xenopus oocytes was studied for several splicing variants of the Drosophia Shaker gene and for several site-directed mutants of this channel. Charybdotoxin blocking affinity is lowered by a factor of 3.5 upon replacing glutamate-422 with glutamine, and by a factor of about 12 upon substituting lysine in this position. Replacement of glutamate-422 by aspartate had no effect on toxin affinity. Thus, the glutamate residue at position 422 of this potassium channel is near or in the externally facing mouth of the potassium conduction pathway, and the positively charged toxin is electrostatically focused toward its blocking site by the negative potential set up by glutamate-422.