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 Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Bioinformatics, Bloomsbury Centre for (Closed), Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 02 Oct 2013 11:13 |
| Last Modified: | 16 Apr 2025 15:44 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/8353 |
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