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

Claire Bagnéris, Paul G. DeCaen, Benjamin A. Hall, Claire E. Naylor, David E. Clapham, Christopher W. M. Kay and B. A. Wallace ()
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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
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
Christopher W. M. Kay: Institute of Structural and Molecular Biology, University College London
B. A. Wallace: School of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, University of London

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3465

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