Voltage-dependent structural changes in voltage-gated sodium channels

该项目旨在深入了解Nav通道所经历的结构重排，Nav通道是动物神经系统的关键组成部分。电压门控钠（Nav）通道在可兴奋细胞中启动动作电位。它们响应膜去极化而打开，然后迅速闭合。真核细胞Nav通道包含四个独特的电压传感器结构域（VSD），控制通道如何响应膜电位变化。最近报道的细菌Nav通道的晶体结构极大地推进了该领域，但这些通道包含四个相同的VSD并且具有不同的失活性质。因此，关于真核细胞Nav通道VSD的构象可塑性还有很多需要了解。该项目计划使用动物毒素捕获处于门控循环定义状态的真核VSD，使用核磁共振和X射线晶体学进行详细的结构分析。

This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to membrane potential changes. Recently reported crystal structures of bacterial Nav channels have greatly advanced the field, but these channels contain four identical VSDs and have different inactivation properties. Thus, much remains to be learnt about the conformational plasticity of eukaryotic Nav channel VSDs. The project plans to use animal toxins to capture eukaryotic VSDs in defined states of the gating cycle for detailed structural analysis using nuclear magnetic resonance and X-ray crystallography.