A repulsion mechanism explains magnesium permeation and selectivity in CorA
A repulsion mechanism explains magnesium permeation and selectivity in CorA
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DOI：
10.1073/pnas.1319054111
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发表时间：
2014-02-25
影响因子：
11.1
通讯作者：
Perozo, Eduardo
中科院分区：
文献类型：
--
作者：
Dalmas, Olivier;Sandtner, Walter;Perozo, Eduardo
镁（Mg 2+）在生物学中起着核心作用，调节许多酶的活性并稳定关键大分子的结构。在细菌中，CorA是Mg 2+摄取的主要来源，并通过细胞内Mg 2+进行自我调节。使用门控突变体在二价离子结合位点，我们能够表征CorA的选择性和渗透性能的一价和二价阳离子灌注双电极电压钳下。目前的数据表明，在生理条件下，CorA是一个多占用Mg 2 +-选择性通道，完全排除一价阳离子，和Ca 2+，而在没有Mg 2+，CorA基本上是非选择性的，显示对其他二价离子只有轻微的偏好（Ca 2 + > Mn 2 + > Co 2 + > Mg 2 + > Ni 2+）。对单价阳离子的选择性通过Mg 2+结合在高亲和力位点发生，该位点由孔的细胞外侧的Gly-Met-Asn特征序列（Gly 312和Asn 314）形成。这种机制是令人想起的排斥模型提出的Ca 2+通道的选择性，尽管在序列和整体结构的差异。
Magnesium (Mg2+) plays a central role in biology, regulating the activity of many enzymes and stabilizing the structure of key macromolecules. In bacteria, CorA is the primary source of Mg2+ uptake and is self-regulated by intracellular Mg2+. Using a gating mutant at the divalent ion binding site, we were able to characterize CorA selectivity and permeation properties to both monovalent and divalent cations under perfused two-electrode voltage clamp. The present data demonstrate that under physiological conditions, CorA is a multioccupancy Mg2+-selective channel, fully excluding monovalent cations, and Ca2+, whereas in absence of Mg2+, CorA is essentially nonselective, displaying only mild preference against other divalents (Ca2+ > Mn2+ > Co2+ > Mg2+ > Ni2+). Selectivity against monovalent cations takes place via Mg2+ binding at a high-affinity site, formed by the Gly-Met-Asn signature sequence (Gly312 and Asn314) at the extracellular side of the pore. This mechanism is reminiscent of repulsion models proposed for Ca2+ channel selectivity despite differences in sequence and overall structure.