Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel
Abstract Mitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg2+ to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the mechanism by which Mrs2 permeates Mg2+ remains unclear. Here, we report four cryo-electron...
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40516-2 |
| _version_ | 1797558555029536768 |
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| author | Ming Li Yang Li Yue Lu Jianhui Li Xuhang Lu Yue Ren Tianlei Wen Yaojie Wang Shenghai Chang Xing Zhang Xue Yang Yuequan Shen |
| author_facet | Ming Li Yang Li Yue Lu Jianhui Li Xuhang Lu Yue Ren Tianlei Wen Yaojie Wang Shenghai Chang Xing Zhang Xue Yang Yuequan Shen |
| author_sort | Ming Li |
| collection | DOAJ |
| description | Abstract Mitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg2+ to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the mechanism by which Mrs2 permeates Mg2+ 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 Mg2+ uptake assays show that the R-ring may function as a charge repulsion barrier, and Cl− may function as a ferry to jointly gate Mg2+ permeation in hMrs2. In addition, the membrane potential is likely to be the driving force for Mg2+ permeation. Our results provide insights into the channel assembly and Mg2+ permeation of hMrs2. |
| first_indexed | 2024-03-10T17:33:06Z |
| format | Article |
| id | doaj.art-f0da641f058c4958b961818bb7a655f2 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:33:06Z |
| publishDate | 2023-08-01 |
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| series | Nature Communications |
| spelling | doaj.art-f0da641f058c4958b961818bb7a655f22023-11-20T09:58:14ZengNature PortfolioNature Communications2041-17232023-08-0114111110.1038/s41467-023-40516-2Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channelMing Li0Yang Li1Yue Lu2Jianhui Li3Xuhang Lu4Yue Ren5Tianlei Wen6Yaojie Wang7Shenghai Chang8Xing Zhang9Xue Yang10Yuequan Shen11State Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityDepartment of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityState Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai UniversityAbstract Mitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg2+ to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the mechanism by which Mrs2 permeates Mg2+ 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 Mg2+ uptake assays show that the R-ring may function as a charge repulsion barrier, and Cl− may function as a ferry to jointly gate Mg2+ permeation in hMrs2. In addition, the membrane potential is likely to be the driving force for Mg2+ permeation. Our results provide insights into the channel assembly and Mg2+ permeation of hMrs2.https://doi.org/10.1038/s41467-023-40516-2 |
| spellingShingle | Ming Li Yang Li Yue Lu Jianhui Li Xuhang Lu Yue Ren Tianlei Wen Yaojie Wang Shenghai Chang Xing Zhang Xue Yang Yuequan Shen Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel Nature Communications |
| title | Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel |
| title_full | Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel |
| title_fullStr | Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel |
| title_full_unstemmed | Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel |
| title_short | Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel |
| title_sort | molecular basis of mg2 permeation through the human mitochondrial mrs2 channel |
| url | https://doi.org/10.1038/s41467-023-40516-2 |
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