Structural model of the open-closed-inactivated cycle of prokaryotic voltage-gated sodium channels.-猫眼课题宝

DOI：

10.1085/jgp.201411242

发表时间：

2015-01

期刊：

The Journal of general physiology

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Bagnéris C;Naylor CE;McCusker EC;Wallace BA

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278185/?report=classic

在可兴奋细胞中，动作电位的起始是由电压门控钠通道的开放引起的。这些通道在打开、关闭和失活状态之间经历一系列构象变化。已经提出了许多模型的结构转换，导致这些不同的功能状态。在这里，我们比较的晶体结构的原核钠通道捕获在不同的构象形式，并使用它们作为基础，检查分子模型的激活，缓慢失活，和恢复过程。我们比较了孔结构域的结构相似性和差异，特别是跨膜螺旋、孔腔内的收缩、最后一个跨膜螺旋细胞质末端的激活门、C末端结构域和选择性过滤器。我们讨论了在以前的打开、关闭和失活模型的背景下观察到的差异，并提出了一个新的基于结构的功能转变模型。我们提出的原核细胞通道激活机制，然后在真核细胞钠通道的激活过渡进行比较。

In excitable cells, the initiation of the action potential results from the opening of voltage-gated sodium channels. These channels undergo a series of conformational changes between open, closed, and inactivated states. Many models have been proposed for the structural transitions that result in these different functional states. Here, we compare the crystal structures of prokaryotic sodium channels captured in the different conformational forms and use them as the basis for examining molecular models for the activation, slow inactivation, and recovery processes. We compare structural similarities and differences in the pore domains, specifically in the transmembrane helices, the constrictions within the pore cavity, the activation gate at the cytoplasmic end of the last transmembrane helix, the C-terminal domain, and the selectivity filter. We discuss the observed differences in the context of previous models for opening, closing, and inactivation, and present a new structure-based model for the functional transitions. Our proposed prokaryotic channel activation mechanism is then compared with the activation transition in eukaryotic sodium channels.