Role of the C-terminal domain in the structure and function of tetrameric sodium channels.
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.
1] School of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck College, University of London, London WC1E 7HX, UK [2].
Claire
C
Bagnéris
Paul G
PG
Decaen
Benjamin A
BA
Hall
Claire E
CE
Naylor
David E
DE
Clapham
Christopher W M
CW
Kay
B A
BA
Wallace
D020561:Alphaproteobacteria / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D055672:Static Electricity; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000235:genetics
D001426:Bacterial Proteins; D011994:Recombinant Proteins; D061566:Voltage-Gated Sodium Channels