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

    Bagneris, Claire and DeCaen, P.G. and Hall, B.A. and Naylor, Claire E. and Clapham, D.E. and Kay, C.W.M. and Wallace, Bonnie A. (2013) Role of the C-terminal domain in the structure and function of tetrameric sodium channels. Nature Communications 4 , p. 2465. ISSN 2041-1723.

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    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.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): Biological sciences, Biophysics, Biochemistry
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Research Centre: Bioinformatics, Bloomsbury Centre for, Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 02 Oct 2013 11:13
    Last Modified: 07 Dec 2016 15:05
    URI: http://eprints.bbk.ac.uk/id/eprint/8353

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