Role of the C-terminal domain in the structure and function of tetrameric sodium channels.
Role of the C-terminal domain in the structure and function of tetrameric sodium channels.
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DOI：
10.1038/ncomms3465
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发表时间：
2013
影响因子：
16.6
通讯作者：
Wallace, B. A.
中科院分区：
文献类型：
--
作者：
Bagneris, Claire;DeCaen, Paul G.;Hall, Benjamin A.;Naylor, Claire E.;Clapham, David E.;Kay, Christopher W. M.;Wallace, B. A.
电压门控钠通道在电信号中起着至关重要的作用。原核钠通道是由跨膜(TM)电压敏感结构域、孔区和细胞质羧基末端结构域组成的四聚体。以往细菌钠通道的晶体结构揭示了其TM结构域的性质，但不揭示其C-末端结构域(CTD)的性质。在这里，使用电子顺磁共振(EPR)谱结合分子动力学，我们证明了来自海洋磁球菌的NavMS通道的CTD包括一个将TM结构域连接到一个四螺旋螺旋线圈束的柔性区域。纳维姆斯孔的2.9cmA分辨率的晶体结构表明了 的位置，这与EPR衍生的结构是一致的。功能分析表明，螺旋线圈结构域将失活与通道开放结合在一起，并由连接区中带负电荷的残基启用。基于这种结构提出了一种浇注机制，由此可以在不需要解开盘管的情况下展开孔底。原核生物电压门控钠通道具有动态无序的细胞质C-末端结构域。Bagnéris等人。介绍了海洋磁球菌Navms孔区和C末端结构域的结构，揭示了其在通道失活和开放耦合中的作用。
Voltage-gated sodium channels have essential roles in electrical signalling. Prokaryotic sodium channels are tetramers consisting of transmembrane (TM) voltage-sensing and pore domains, and a cytoplasmic carboxy-terminal domain. Previous crystal structures of bacterial sodium channels revealed the nature of their TM domains but not their C-terminal domains (CTDs). Here, using electron paramagnetic resonance (EPR) spectroscopy combined with molecular dynamics, we show that the CTD of the NavMs channel from Magnetococcus marinus includes a flexible region linking the TM domains to a four-helix coiled-coil bundle. A 2.9 Å resolution crystal structure of the NavMs pore indicates the position of the CTD, which is consistent with the EPR-derived structure. Functional analyses demonstrate that the coiled-coil domain couples inactivation with channel opening, and is enabled by negatively charged residues in the linker region. A mechanism for gating is proposed based on the structure, whereby splaying of the bottom of the pore is possible without requiring unravelling of the coiled-coil. Prokaryotic voltage-gated sodium channels possess dynamically disordered cytoplasmic C-terminal domains. Bagnéris et al. present the structure of the Magnetococcus marinus NavMs pore and C-terminal domain and reveal its role in coupling channel inactivation and opening.
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影响因子：
64.8
作者：
Payandeh, Jian;El-Din, Tamer M. Gamal;Scheuer, Todd;Zheng, Ning;Catterall, William A.
通讯作者：
Catterall, William A.
DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
影响因子：
16.2
作者：
Howard, Rebecca J.;Clark, Kimberly A.;Minor, Daniel L., Jr.
通讯作者：
Minor, Daniel L., Jr.
影响因子：
2.9
作者：
Nurani, Ghasem;Radford, Matthew;Wallace, B. A.
通讯作者：
Wallace, B. A.
DOI：
10.1074/jbc.c111.228122
发表时间：
2011-05-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
McCusker EC;D'Avanzo N;Nichols CG;Wallace BA
通讯作者：
Wallace BA