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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Allosteric gating mechanism underlies the flexible gating of KCNQ1 potassium channels
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Allosteric gating mechanism underlies the flexible gating of KCNQ1 potassium channels

机译:变构门控机制是KCNQ1钾通道灵活门控的基础

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KCNQ1 (Kv7.1) is a unique member of the superfamily of voltage-gated K+ channels in that it displays a remarkable range of gating behaviors tuned by coassembly with different p subunits of the KCNE family of proteins. To better understand the basis for the biophysical diversity of KCNQ1 channels, we here investigate the basis of KCNQ1 gating in the absence of β subunits using voltage-clamp fluorometry (VCF). In our previous study, we found the kinetics and voltage dependence of voltage-sensor movements are very similai to those of the channel gate, as if multiple voltage-sensor movements are not required to precede gate opening. Here, we have tested two different hypotheses to explain KCNQ1 gating: (i) KCNQ1 voltage sensors undergo a single concerted movement thai leads to channel opening, or (ii) individual voltage-sensor movements lead to channel opening before all voltage sensors have moved. Here, we find that KCNQ1 voltage sensors move relatively independently, but that the channel can conduct before all voltage sensors have activated. We explore a KCNQ1 point mutation that causes some channels to transition to the open state even in the absence of voltage-sensor movement. To interpret these results, we adopt an allosteric gating scheme wherein KCNQ1 is able tc transition to the open state after zero to four voltage-sensor movements. This model allows for widely varying gating behavior depending on the relative strength of the opening transition, and suggests how KCNQ1 could be controlled by coassembly with different KCNE family members.
机译:KCNQ1(Kv7.1)是电压门控K +通道超家族的独特成员,因为它通过与KCNE蛋白质家族的不同p亚基共装配而调节了一系列显着的门控行为。为了更好地了解KCNQ1通道生物物理多样性的基础,我们在这里使用电压钳荧光(VCF)研究了在不存在β亚基的情况下KCNQ1门控的基础。在我们之前的研究中,我们发现电压传感器运动的动力学和电压依赖性与通道门的动力学和动力学非常相似,好像在栅极打开之前不需要多次电压传感器运动。在这里,我们测试了两种不同的假设来解释KCNQ1门控:(i)KCNQ1电压传感器经过一次一致的运动导致通道打开,或者(ii)各个电压传感器的运动导致了所有电压传感器移动之前的通道打开。在这里,我们发现KCNQ1电压传感器相对独立地移动,但是通道可以在所有电压传感器激活之前导通。我们探索了一个KCNQ1点突变,即使在没有电压传感器运动的情况下,该突变也会导致某些通道过渡到打开状态。为了解释这些结果,我们采用了一种变构门控方案,其中KCNQ1在零到四次电压传感器运动之后能够tc过渡到开路状态。该模型允许根据打开过渡的相对强度在很大范围内改变门控行为,并建议如何通过与不同的KCNE家族成员共同组装来控制KCNQ1。

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