Role of the C-terminal domain in the structure and function of tetrameric sodium channels
Hall, Benjamin A.
Naylor, Claire E.
Kay, Christopher W. M.
Wallace, B. A.
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CitationBagnéris, Claire, Paul G. DeCaen, Benjamin A. Hall, Claire E. Naylor, David E. Clapham, Christopher W. M. Kay, and B. A. Wallace. 2013. “Role of the C-terminal domain in the structure and function of tetrameric sodium channels.” Nature Communications 4 (1): 2465. doi:10.1038/ncomms3465. http://dx.doi.org/10.1038/ncomms3465.
AbstractVoltage-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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11878805