• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Springer Open Choice >Gating mechanism of Kv11.1 (hERG) K+ channels without covalent connection between voltage sensor and pore domains
【2h】

Gating mechanism of Kv11.1 (hERG) K+ channels without covalent connection between voltage sensor and pore domains

机译：Kv11.1（hERG）K +通道的门控机制电压传感器和孔域之间没有共价连接

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Kv11.1 (hERG, KCNH2) is a voltage-gated potassium channel crucial in setting the cardiac rhythm and the electrical behaviour of several non-cardiac cell types. Voltage-dependent gating of Kv11.1 can be reconstructed from non-covalently linked voltage sensing and pore modules (split channels), challenging classical views of voltage-dependent channel activation based on a S4–S5 linker acting as a rigid mechanical lever to open the gate. Progressive displacement of the split position from the end to the beginning of the S4–S5 linker induces an increasing negative shift in activation voltage dependence, a reduced z g value and a more negative ΔG 0 for current activation, an almost complete abolition of the activation time course sigmoid shape and a slowing of the voltage-dependent deactivation. Channels disconnected at the S4–S5 linker near the S4 helix show a destabilization of the closed state(s). Furthermore, the isochronal ion current mode shift magnitude is clearly reduced in the different splits. Interestingly, the progressive modifications of voltage dependence activation gating by changing the split position are accompanied by a shift in the voltage-dependent availability to a methanethiosulfonate reagent of a Cys introduced at the upper S4 helix. Our data demonstrate for the first time that alterations in the covalent connection between the voltage sensor and the pore domains impact on the structural reorganizations of the voltage sensor domain. Also, they support the hypothesis that the S4–S5 linker integrates signals coming from other cytoplasmic domains that constitute either an important component or a crucial regulator of the gating machinery in Kv11.1 and other KCNH channels.Electronic supplementary materialThe online version of this article (10.1007/s00424-017-2093-9) contains supplementary material, which is available to authorized users.
机译：Kv11.1（hERG，KCNH2）是一个电压门控钾离子通道，对设定心律和几种非心脏细胞类型的电行为至关重要。可以从非共价链接的电压感应和孔模块（分裂通道）重建Kv11.1的电压依赖性门控，挑战了基于S4–S5连接器作为刚性机械杠杆来打开的电压依赖性通道激活的经典观点大门。从S4–S5接头的末端到末端逐渐分开的位置引起激活电压依赖性的负移增加，zg值降低和电流激活的ΔG0更大，几乎完全取消了激活时间当然是S形，并会减慢电压相关的失活。在S4螺旋附近的S4–S5接头处断开的通道显示了闭合状态的不稳定。此外，在不同的分割中，等时离子电流模式偏移幅度明显减小。有趣的是，通过改变分裂位置对电压依赖性活化门控的逐步修饰伴随着电压依赖性可用性向在上部S4螺旋处引入的Cys的甲硫代磺酸盐试剂的转移。我们的数据首次证明了电压传感器和孔结构域之间共价连接的改变会影响电压传感器结构域的结构重组。同样，它们支持S4–S5接头整合了来自其他胞质域的信号的假设，这些胞质域构成了Kv11.1和其他KCNH通道中门控机制的重要组成部分或至关重要的调节剂。电子补充材料本文的在线版本（10.1007 / s00424-017-2093-9）包含补充材料，授权用户可以使用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号