Glass William G, Duncan Anna L, Biggin Philip C
Structural Bioinformatics and Computational Biochemistry, Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Front Mol Biosci. 2020 Mar 18;7:40. doi: 10.3389/fmolb.2020.00040. eCollection 2020.
Voltage-gated sodium (Na ) channels form the basis for the initiation of the action potential in excitable cells by allowing sodium ions to pass through the cell membrane. The Na channel α subunit is known to function both with and without associated β subunits. There is increasing evidence that these β subunits have multiple roles that include not only influencing the voltage-dependent gating but also the ability to alter the spatial distribution of the pore-forming α subunit. Recent structural data has shown possible ways in which β1 subunits may interact with the α subunit. However, the position of the β1 subunit would not be compatible with a previous trimer structure of the β3 subunit. Furthermore, little is currently known about the dynamic behavior of the β subunits both as individual monomers and as higher order oligomers. Here, we use multiscale molecular dynamics simulations to assess the dynamics of the β3, and the closely related, β1 subunit. These findings reveal the spatio-temporal dynamics of β subunits and should provide a useful framework for interpreting future low-resolution experiments such as atomic force microscopy.
电压门控钠（Na⁺）通道通过允许钠离子穿过细胞膜，构成了可兴奋细胞中动作电位起始的基础。已知Na⁺通道α亚基在有或没有相关β亚基的情况下均可发挥作用。越来越多的证据表明，这些β亚基具有多种作用，不仅包括影响电压依赖性门控，还包括改变形成孔道的α亚基的空间分布的能力。最近的结构数据显示了β1亚基可能与α亚基相互作用的方式。然而，β1亚基的位置与先前β3亚基的三聚体结构不兼容。此外，目前对于β亚基作为单个单体和更高阶寡聚体的动态行为知之甚少。在这里，我们使用多尺度分子动力学模拟来评估β3以及密切相关的β1亚基的动力学。这些发现揭示了β亚基的时空动力学，应为解释未来的低分辨率实验（如原子力显微镜）提供有用的框架。
