The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel
The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel
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DOI：
10.1016/s0092-8674(00)00088-x
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发表时间：
2000-09-01
期刊：
影响因子：
64.5
通讯作者：
Berger, JM
中科院分区：
文献类型：
--
作者：
Minor, DL;Lin, YF;Berger, JM
KV电压门控钾通道共用一个细胞质组装结构域T1。最近两个T1 C-末端环残基的突变表明T1参与了通道门控。然而，这些突变体的结构变化留下了关于T1直接参与门控的问题。我们在哺乳动物Kv1.2中发现，门控严重依赖于异常极性界面中互补T1表面的残基。该界面上的等位变异在稳定给药通道和增加T1四聚体稳定性的同时，几乎不会引起结构变化。用四聚螺旋线圈代替T1会破坏闭合通道的稳定性。总之，这些数据表明，涉及埋藏的极性T1表面的结构变化在导致通道开放的构象变化中起着关键作用。
Kv voltage-gated potassium channels share a cytoplasmic assembly domain, T1. Recent mutagenesis of two T1 C-terminal loop residues implicates T1 in channel gating. However, structural alterations of these mutants leave open the question concerning direct involvement of T1 in gating. We find in mammalian Kv1.2 that gating depends critically on residues at complementary T1 surfaces in an unusually polar interface. An isosteric mutation in this interface causes surprisingly little structural alteration while stabilizing the dosed channel and increasing the stability of T1 tetramers. Replacing T1 with a tetrameric coiled-coil destabilizes the closed channel. Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening.