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Role of the C-terminal domain in the structure and function of tetrameric sodium channels

Author

Listed:
  • Claire Bagnéris

    (School of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, University of London)

  • Paul G. DeCaen

    (Howard Hughes Medical Institute, Children’s Hospital Boston
    Harvard Medical School)

  • Benjamin A. Hall

    (Microsoft Research Cambridge)

  • Claire E. Naylor

    (School of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, University of London)

  • David E. Clapham

    (Howard Hughes Medical Institute, Children’s Hospital Boston
    Harvard Medical School)

  • Christopher W. M. Kay

    (Institute of Structural and Molecular Biology, University College London
    London Centre for Nanotechnology, University College London)

  • B. A. Wallace

    (School of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, University of London)

Abstract

Voltage-gated sodium channels have essential roles in electrical signalling. Prokaryotic sodium channels are tetramers consisting of transmembrane (TM) voltage-sensing and pore domains, and a cytoplasmic carboxy-terminal domain. Previous crystal structures of bacterial sodium channels revealed the nature of their TM domains but not their C-terminal domains (CTDs). Here, using electron paramagnetic resonance (EPR) spectroscopy combined with molecular dynamics, we show that the CTD of the NavMs channel from Magnetococcus marinus includes a flexible region linking the TM domains to a four-helix coiled-coil bundle. A 2.9 Å resolution crystal structure of the NavMs pore indicates the position of the CTD, which is consistent with the EPR-derived structure. Functional analyses demonstrate that the coiled-coil domain couples inactivation with channel opening, and is enabled by negatively charged residues in the linker region. A mechanism for gating is proposed based on the structure, whereby splaying of the bottom of the pore is possible without requiring unravelling of the coiled-coil.

Suggested Citation

  • Claire Bagnéris & Paul G. DeCaen & Benjamin A. Hall & Claire E. Naylor & David E. Clapham & Christopher W. M. Kay & B. A. Wallace, 2013. "Role of the C-terminal domain in the structure and function of tetrameric sodium channels," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3465
    DOI: 10.1038/ncomms3465
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    Cited by:

    1. Ravi Dhiman & Rehani S. Perera & Chetan S. Poojari & Haakon T. A. Wiedemann & Reinhard Kappl & Christopher W. M. Kay & Jochen S. Hub & Bianca Schrul, 2024. "Hairpin protein partitioning from the ER to lipid droplets involves major structural rearrangements," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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