Lunin Vladimir V, Dobrovetsky Elena, Khutoreskaya Galina, Zhang Rongguang, Joachimiak Andrzej, Doyle Declan A, Bochkarev Alexey, Maguire Michael E, Edwards Aled M, Koth Christopher M
Department of Medical Biophysics, University of Toronto, 112 College Street, Toronto, Ontario M5G 1L6, Canada.
Nature. 2006 Apr 6;440(7085):833-7. doi: 10.1038/nature04642.
The magnesium ion, Mg2+, is essential for myriad biochemical processes and remains the only major biological ion whose transport mechanisms remain unknown. The CorA family of magnesium transporters is the primary Mg2+ uptake system of most prokaryotes and a functional homologue of the eukaryotic mitochondrial magnesium transporter. Here we determine crystal structures of the full-length Thermotoga maritima CorA in an apparent closed state and its isolated cytoplasmic domain at 3.9 A and 1.85 A resolution, respectively. The transporter is a funnel-shaped homopentamer with two transmembrane helices per monomer. The channel is formed by an inner group of five helices and putatively gated by bulky hydrophobic residues. The large cytoplasmic domain forms a funnel whose wide mouth points into the cell and whose walls are formed by five long helices that are extensions of the transmembrane helices. The cytoplasmic neck of the pore is surrounded, on the outside of the funnel, by a ring of highly conserved positively charged residues. Two negatively charged helices in the cytoplasmic domain extend back towards the membrane on the outside of the funnel and abut the ring of positive charge. An apparent Mg2+ ion was bound between monomers at a conserved site in the cytoplasmic domain, suggesting a mechanism to link gating of the pore to the intracellular concentration of Mg2+.
镁离子(Mg2+)对于众多生化过程至关重要,并且仍然是唯一一种其转运机制尚不清楚的主要生物离子。镁转运蛋白的CorA家族是大多数原核生物的主要Mg2+摄取系统,也是真核线粒体镁转运蛋白的功能同源物。在这里,我们分别以3.9 Å和1.85 Å的分辨率确定了处于明显关闭状态的全长嗜热栖热菌CorA及其分离的细胞质结构域的晶体结构。该转运蛋白是一个漏斗形的同五聚体,每个单体有两个跨膜螺旋。通道由内部的五个螺旋组成,推测由庞大的疏水残基门控。大的细胞质结构域形成一个漏斗,其宽口指向细胞内部,其壁由五个长螺旋形成,这些长螺旋是跨膜螺旋的延伸。孔的细胞质颈部在漏斗外部被一圈高度保守的带正电荷的残基包围。细胞质结构域中的两个带负电荷的螺旋在漏斗外部向膜延伸并邻接正电荷环。在细胞质结构域的一个保守位点,一个明显的Mg2+离子结合在单体之间,这表明了一种将孔的门控与细胞内Mg2+浓度联系起来的机制。