通道CORA的冷电磁结构揭示了门时的对称性断裂

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Doreen Matthies¹, Olivier Dalmas², Mario J Borgnia¹

¹Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Cell

|February 13, 2016

概括

作为 prokaryotes 中的关键转运体的 CorA 通过显著的结构变化来打开和关闭. 这种离子通道封闭机制由冷电磁探测揭示,可能适用于类似的离子通道.

科学领域:

结构生物学
生物物理
分子生物学

背景情况:

甲基是 prokaryotes 中的主要离子 (Mg2+) 吸收系统.
细胞内Mg2+度调节了CoraA的发生,分离常数 (KD) 约为1-2mM.
之前的X射线结晶学和EPR光谱学表明了形状变化,但缺乏高分辨率的门机制结构细节.

研究的目的:

通过确定不同功能状态的高分辨率结构来阐明CORA的结构基础.
为了可视化CORA在Mg2+结合和释放时的形态转变.
了解Mg2+调节CORA通道的开关机制.

主要方法:

使用冷电子显微镜 (cryo-EM) 来确定CORA的结构.
对Mg2+结合的闭合形态和两个不同的Mg2+无开放状态的结构进行了解析.
在3.8 Å和7.1 Å获得了高分辨率的结构数据.

主要成果:

Mg2+结合状态显示出一个封闭的5倍对称形状.
在没有Mg2+的情况下,Cora采用了一组开放的,不对称的状态.
五个子单元中的四个通过链式运动 (高达35°) 经历了显著的位移,从封闭状态过渡到开放状态.
这种转变凸显了CORA的动态性质.

结论:

在Mg2+解离过程中,CorA门的特征是从单一的封闭状态转变为一个开放的,不对称的状态.
观察到的大型子单元位移和链式运动是CORA门的关键结构特征.
这种依赖Mg2+的门机制很可能保留在其他结构相关的双价离子通道中.

关键词:

不对称性形状的变化直接电子探测器离子通道膜蛋白结构单粒子冷电子显微镜

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