Mg2+-sensing mechanism of Mg2+ transporter MgtE probed by molecular dynamics study
Mg2+-sensing mechanism of Mg2+ transporter MgtE probed by molecular dynamics study
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DOI：
10.1073/pnas.0802991105
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发表时间：
2008-10-07
影响因子：
11.1
通讯作者：
Nureki, Osamu
中科院分区：
文献类型：
--
作者：
Ishitani, Ryuichiro;Sugita, Yuji;Nureki, Osamu
细胞内离子浓度的适当调节对于维持生命是必不可少的，并且通过以严格调节的方式将其底物运输穿过膜的离子转运蛋白来实现。MgtE是一种Mg 2+转运蛋白，可能在细胞内Mg 2+浓度的稳态中起作用。最近的晶体学研究表明，其胞质结构域经历了Mg2+依赖性的结构变化，这被提议门控通过跨膜结构域的离子传导孔。然而，Mg2+传感的动力学，即，MgtE如何响应细胞内Mg 2+浓度的变化仍然是难以捉摸的。在这里，我们进行了分子动力学模拟的MgtE胞质结构域。模拟成功地再现了结合或释放Mg 2+时胞质结构域的结构变化，以及离子选择性。这些结果表明IN和CBS结构域在胞质结构域和它们各自的Mg 2+结合位点中的作用。结合目前的晶体结构，我们提出了一个原子级的详细模型，MgtE的Mg2+传感。
Proper regulation of the intracellular ion concentration is essential to maintain life and is achieved by ion transporters that transport their substrates across the membrane in a strictly regulated manner. MgtE is a Mg2+ transporter that may function in the homeostasis of the intracellular Mg2+ concentration. A recent crystallographic study revealed that its cytosolic domain undergoes a Mg2+-dependent structural change, which is proposed to gate the ion-conducting pore passing through the transmembrane domain. However, the dynamics of Mg2+ sensing, i.e., how MgtE responds to the change in the intracellular Mg2+ concentration, remained elusive. Here we performed molecular dynamics simulations of the MgtE cytosolic domain. The simulations successfully reproduced the structural changes of the cytosolic domain upon binding or releasing Mg2+, as well as the ion selectivity. These results suggested the roles of the IN and CBS domains in the cytosolic domain and their respective Mg2+ binding sites. Combined with the current crystal structures, we propose an atomically detailed model of Mg2+ sensing by MgtE.