A positive charge at the N-terminal segment of Discrepin increases the blocking effect of K+ channels responsible for the IA currents in cerebellum granular cells
A positive charge at the N-terminal segment of Discrepin increases the blocking effect of K+ channels responsible for the IA currents in cerebellum granular cells
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DOI：
10.1016/j.bbagen.2008.01.012
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发表时间：
2008-04-01
影响因子：
3
通讯作者：
Possani, Lourival D.
中科院分区：
文献类型：
--
作者：
Romeo, Stefania;Corzo, Gerardo;Possani, Lourival D.
Discrepin是一种蝎肽，优先阻断大鼠小脑颗粒细胞电压依赖性K+通道的I-A电流。它是从钳蝎Tityus discrepans的毒液中分离出来的，含有38个氨基酸残基，在N-末端位点有一个焦谷氨酸。Discrepin具有最低的序列同一性（约100%）。50%）中的六个成员的α-KTx 15亚家族的蝎毒素。为了找出哪些残基对于Discrepin的阻断作用是重要的，化学合成了六个突变体（V6 K、I19 R、D20 K、T35 v、I19 R-D20 K、I19 R-D20 K-R21 V），正确折叠并检查了它们的生理特性。残基V6和D20取代基本上带电荷的氨基酸增加了Discrepin的阻断活性，特别是毒素N-末端区段的突变V6 K。突变体V6 K和D20 K的三维结构模型的分析支持碱性残基提高其阻断活性的想法，类似于BmTx 3的情况，BmTx 3是一种从东亚钳蝎中获得的毒性肽，其对大鼠小脑颗粒细胞K+通道中的I-A电流具有最高的已知阻断作用。(C)2008 Elsevier B. V.保留所有权利。
Discrepin is a scorpion peptide that blocks preferentially the I-A currents of the voltage-dependent K+ channel of rat cerebellum granular cells. It was isolated from the venom of the buthid scorpion Tityus discrepans and contains 38 amino acid residues with a pyroglutamic acid at the N-terminal site. Discrepin has the lowest sequence identity (approx. 50%) among the six members of the alpha-KTx15 sub-family of scorpion toxins. In order to find out which residues are important for the blocking effects of Discrepin, six mutants were chemically synthesized (V6K, I19R, D20K, T35v, I19R-D20K, I19R-D20K-R21V), correctly folded and their physiological properties were examined. Substitution of residues V6 and D20 for basically charged amino acids increases the blocking activity of Discrepin, specially the mutation V6K at the N-terminal segment of the toxin. Analysis of 3D-structure models of the mutants V6K and D20K supports the idea that basic residues improve their blocking activities, similarly to what happens with BmTx3, a toxic peptide obtained from Buthus martensi scorpion, which has the highest known blocking effects of I-A currents in K+ channels of rat cerebellum granular cells. (C) 2008 Elsevier B.V. All rights reserved.