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

Author

Listed:
  • Ming Li

    (Nankai University)

  • Yang Li

    (Nankai University)

  • Yue Lu

    (Nankai University)

  • Jianhui Li

    (Nankai University)

  • Xuhang Lu

    (Nankai University)

  • Yue Ren

    (Nankai University)

  • Tianlei Wen

    (Nankai University)

  • Yaojie Wang

    (Nankai University)

  • Shenghai Chang

    (Zhejiang University
    Zhejiang University)

  • Xing Zhang

    (Zhejiang University
    Zhejiang University)

  • Xue Yang

    (Nankai University)

  • Yuequan Shen

    (Nankai University)

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.

Suggested Citation

  • Ming Li & Yang Li & Yue Lu & Jianhui Li & Xuhang Lu & Yue Ren & Tianlei Wen & Yaojie Wang & Shenghai Chang & Xing Zhang & Xue Yang & Yuequan Shen, 2023. "Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40516-2
    DOI: 10.1038/s41467-023-40516-2
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    References listed on IDEAS

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    1. Cornelius Gati & Artem Stetsenko & Dirk J. Slotboom & Sjors H. W. Scheres & Albert Guskov, 2017. "The structural basis of proton driven zinc transport by ZntB," Nature Communications, Nature, vol. 8(1), pages 1-8, December.
    2. Olivier Dalmas & Pornthep Sompornpisut & Francisco Bezanilla & Eduardo Perozo, 2014. "Molecular mechanism of Mg2+-dependent gating in CorA," Nature Communications, Nature, vol. 5(1), pages 1-11, May.
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    Cited by:

    1. Louis Tung Faat Lai & Jayashree Balaraman & Fei Zhou & Doreen Matthies, 2023. "Cryo-EM structures of human magnesium channel MRS2 reveal gating and regulatory mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Yanan Li & Yonghua Wu & Ru Xu & Jialing Guo & Fenglei Quan & Yongyuan Zhang & Di Huang & Yiran Pei & Hua Gao & Wei Liu & Junjie Liu & Zhenzhong Zhang & Ruijie Deng & Jinjin Shi & Kaixiang Zhang, 2023. "In vivo imaging of mitochondrial DNA mutations using an integrated nano Cas12a sensor," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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    1. Louis Tung Faat Lai & Jayashree Balaraman & Fei Zhou & Doreen Matthies, 2023. "Cryo-EM structures of human magnesium channel MRS2 reveal gating and regulatory mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
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