Crystal structure of the MgtE Mg2+ transporter
Crystal structure of the MgtE Mg2+ transporter
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DOI：
10.1038/nature06093
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发表时间：
2007-08-30
期刊：
影响因子：
64.8
通讯作者：
Nureki, Osamu
中科院分区：
文献类型：
--
作者：
Hattori, Motoyuki;Tanaka, Yoshiki;Nureki, Osamu
镁离子Mg 2+是参与许多生理过程的重要元素。Mg ~（2+）的水合半径最大，离子半径最小。Mg 2+转运蛋白如何选择性地识别和转运大的、完全水合的Mg 2+阳离子仍然不清楚（1）。最近报道了CorA Mg 2+转运蛋白（2-5）的晶体结构（6-8）。Mg 2+转运蛋白的MgtE家族普遍分布于所有系统发育域中（9-11），并且人类同源物已被功能性表征并被认为参与镁稳态（12-14）。然而，MgtE转运蛋白尚未得到彻底表征。在这里，我们确定的晶体结构的全长嗜热栖热菌MgtE在3.5埃的分辨率，并在2.3埃和3.9埃的分辨率的Mg 2+的存在和不存在的胞质结构域，分别。该转运蛋白采用同源二聚体结构，由羧基末端的五个跨膜结构域和氨基末端的胞质结构域组成，所述胞质结构域由超螺旋N结构域和串联重复的胱硫醚-β-合酶结构域组成。一个溶剂可访问的孔几乎穿越跨膜结构域，一个潜在的Mg 2+结合到孔内的保守的Asp 432。来自两个亚基的跨膜（TM）5螺旋通过与连接胱硫醚-β-合酶和跨膜结构域的“连接螺旋”的相互作用关闭孔。四个推定的Mg 2+离子结合在连接螺旋和其他域之间的界面处，这可能锁定孔的闭合构象。两种状态的胞质结构域的结构比较表明Mg 2+依赖的运动的连接螺旋，这可能会重组跨膜螺旋打开孔。这些结果表明，稳态机制，其中Mg 2+之间的胞质结构域的约束调节Mg 2+流量通过传感细胞内Mg 2+浓度。这种假定的调节是否控制离子通道的门控或次级主动转运蛋白的开放仍有待确定。
The magnesium ion Mg2+ is a vital element involved in numerous physiological processes. Mg2+ has the largest hydrated radius among all cations, whereas its ionic radius is the smallest. It remains obscure how Mg2+ transporters selectively recognize and dehydrate the large, fully hydrated Mg2+ cation for transport(1). Recently the crystal structures of the CorA Mg2+ transporter(2-5) were reported(6-8). The MgtE family of Mg2+ transporters is ubiquitously distributed in all phylogenetic domains(9-11), and human homologues have been functionally characterized and suggested to be involved in magnesium homeostasis(12-14). However, the MgtE transporters have not been thoroughly characterized. Here we determine the crystal structures of the full-length Thermus thermophilus MgtE at 3.5 angstrom resolution, and of the cytosolic domain in the presence and absence of Mg2+ at 2.3 angstrom and 3.9 angstrom resolutions, respectively. The transporter adopts a homodimeric architecture, consisting of the carboxy-terminal five transmembrane domains and the amino-terminal cytosolic domains, which are composed of the superhelical N domain and tandemly repeated cystathionine-beta-synthase domains. A solvent-accessible pore nearly traverses the transmembrane domains, with one potential Mg2+ bound to the conserved Asp 432 within the pore. The transmembrane (TM)5 helices from both subunits close the pore through interactions with the 'connecting helices', which connect the cystathionine-beta-synthase and transmembrane domains. Four putative Mg2+ ions are bound at the interface between the connecting helices and the other domains, and this may lock the closed conformation of the pore. A structural comparison of the two states of the cytosolic domains showed the Mg2+-dependent movement of the connecting helices, which might reorganize the transmembrane helices to open the pore. These findings suggest a homeostasis mechanism, in which Mg2+ bound between cytosolic domains regulates Mg2+ flux by sensing the intracellular Mg2+ concentration. Whether this presumed regulation controls gating of an ion channel or opening of a secondary active transporter remains to be determined.