Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel

作者：Ming Li, Yang Li, Yue Lu, Jianhui Li, Xuhang Lu, Yue Ren, Tianlei Wen, Yaojie Wang, Shenghai Chang, Xing Zhang, Xue Yang, Yuequan Shen · 发表于：Nature Communications · 年份：2023 · DOI：10.1038/s41467-023-40516-2 · 被引用次数：25 · 研究领域：Mitochondrial Function and Pathology、ATP Synthase and ATPases Research、RNA and protein synthesis mechanisms

Abstract Mitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg 2+ to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the mechanism by which Mrs2 permeates Mg 2+ remains unclear. Here, we report four cryo-electron microscopy (cryo-EM) reconstructions of Homo sapiens Mrs2 (hMrs2) under various conditions. All of these hMrs2 structures form symmetrical pentamers with very similar pentamer and protomer conformations. A special structural feature of Cl − -bound R-ring, which consists of five Arg332 residues, was found in the hMrs2 structure. Molecular dynamics simulations and mitochondrial Mg 2+ uptake assays show that the R-ring may function as a charge repulsion barrier, and Cl − may function as a ferry to jointly gate Mg 2+ permeation in hMrs2. In addition, the membrane potential is likely to be the driving force for Mg 2+ permeation. Our results provide insights into the channel assembly and Mg 2+ permeation of hMrs2.