...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Calcium-dependent regulation of the voltage-gated sodium channel hH1: Intrinsic and extrinsic sensors use a common molecular switch
【24h】

Calcium-dependent regulation of the voltage-gated sodium channel hH1: Intrinsic and extrinsic sensors use a common molecular switch

机译：钙离子调节的电压门控钠通道hH1的调节：本征和非本征传感器使用共同的分子开关

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The function of the human cardiac voltage-gated sodium channel Nav1.5 (hH1) is regulated in part by binding of calcium to an EF hand in the C-terminal cytoplasmic domain. hH1 is also regulated via an extrinsic calcium-sensing pathway mediated by calmodulin (CaM) via binding to an IQ motif immediately adjacent to the EF-hand domain. The intrinsic EF-hand domain is shown here to interact with the IQ motif, which controls calcium affinity. Remarkably, mutation of the IQ residues has only a minor effect on CaM affinity but drastically reduces calcium affinity of the EF-hand domain, whereas the Brugada mutation A1924T significantly reduces CaM affinity but has no effect on calcium affinity of the EF-hand domain. Moreover, the differences in the biochemical effects of the mutations directly correlate with contrasting effects on channel electrophysiology. A comprehensive model is proposed in which the hH1 IQ motif serves as a molecular switch, coupling the intrinsic and extrinsic calcium sensors.
机译：人的心脏电压门控钠通道Nav1.5（hH1）的功能部分受钙结合到C末端胞质域中的EF手的调节。 hH1还通过钙调蛋白（CaM）介导的外在钙敏感途径进行调控，该途径通过与紧邻EF手结构域的IQ基序结合而实现。此处显示了内在的EF手结构域与控制钙亲和力的IQ基序相互作用。引人注目的是，IQ残基的突变对CaM亲和力只有很小的影响，但大大降低了EF手结构域的钙亲和力，而Brugada突变A1924T显着降低了CaM亲和力，但对EF手结构域的钙亲和力没有影响。此外，突变的生化效应的差异与通道电生理学的对比效应直接相关。提出了一个综合模型，其中hH1 IQ基序充当分子开关，耦合了内在和外在的钙传感器。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

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