Zeinert Rilee, Zhou Fei, Franco Pedro, Zöller Jonathan, Madni Zaid K, Lessen Henry, Aravind L, Langer Julian D, Sodt Alexander J, Storz Gisela, Matthies Doreen
Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Unit on Structural Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Nat Struct Mol Biol. 2025 Jun 23. doi: 10.1038/s41594-025-01593-7.
Magnesium (Mg) uptake systems are present in all domains of life, consistent with the vital role of this ion. P-type ATPase Mg importers are required for bacterial growth when Mg is limiting or during pathogenesis. However, insights into their mechanisms of action are missing. Here we solved the cryo-EM structure of the Mg transporter MgtA from Escherichia coli. We obtained high-resolution structures of both homodimeric (2.9 Å) and monomeric (3.6 Å) forms. The dimer structure is formed by multiple contacts between residues in adjacent soluble N and P subdomains. Our structures revealed an ion, assigned as Mg, in the transmembrane segment. Moreover, we detected two cytoplasmic ion-binding sites and determined the structure of the N-terminal tail. Sequence conservation, mutagenesis and ATPase assays indicate dimerization, the ion-binding sites and the N-terminal tail facilitate cation transport or serve regulatory roles.
镁（Mg）摄取系统存在于生命的所有领域，这与该离子的重要作用相一致。当镁有限或在发病过程中，P型ATP酶镁导入器是细菌生长所必需的。然而，对其作用机制的深入了解尚缺。在此，我们解析了来自大肠杆菌的镁转运蛋白MgtA的冷冻电镜结构。我们获得了同二聚体（2.9 Å）和单体（3.6 Å）形式的高分辨率结构。二聚体结构由相邻可溶性N和P亚结构域中的残基之间的多个接触形成。我们的结构在跨膜段揭示了一个被指定为镁的离子。此外，我们检测到两个胞质离子结合位点并确定了N端尾巴的结构。序列保守性、诱变和ATP酶分析表明二聚化、离子结合位点和N端尾巴促进阳离子转运或发挥调节作用。
