Bagnéris, Claire

Clapham, David E

Decaen, Paul G

Hall, Benjamin

Kay, Christopher WM

Naylor, Claire E

Wallace, BA

English

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

Hall, Benjamin A

Apollo (Cambridge)

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

https://www.repository.cam.ac.uk/bitstream/1810/302129/1/Role%20of%20the%20C-terminal%20domain%20in%20the%20structure%20and%20function%20of%20tetrameric%20sodium%20channels.pdf

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

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