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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 n...

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Autores principales: Bagnéris, Claire, DeCaen, Paul G., Hall, Benjamin A., Naylor, Claire E., Clapham, David E., Kay, Christopher W. M., Wallace, B. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791462/
https://www.ncbi.nlm.nih.gov/pubmed/24051986
http://dx.doi.org/10.1038/ncomms3465
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author Bagnéris, Claire
DeCaen, Paul G.
Hall, Benjamin A.
Naylor, Claire E.
Clapham, David E.
Kay, Christopher W. M.
Wallace, B. A.
author_facet Bagnéris, Claire
DeCaen, Paul G.
Hall, Benjamin A.
Naylor, Claire E.
Clapham, David E.
Kay, Christopher W. M.
Wallace, B. A.
author_sort Bagnéris, Claire
collection PubMed
description 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.
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spelling pubmed-37914622013-10-09 Role of the C-terminal domain in the structure and function of tetrameric sodium channels Bagnéris, Claire DeCaen, Paul G. Hall, Benjamin A. Naylor, Claire E. Clapham, David E. Kay, Christopher W. M. Wallace, B. A. Nat Commun Article 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. Nature Pub. Group 2013-09-19 /pmc/articles/PMC3791462/ /pubmed/24051986 http://dx.doi.org/10.1038/ncomms3465 Text en Copyright © 2013, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/3.0/ This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this licence visit http://creativecommons.org/licenses/by/3.0/.
spellingShingle Article
Bagnéris, Claire
DeCaen, Paul G.
Hall, Benjamin A.
Naylor, Claire E.
Clapham, David E.
Kay, Christopher W. M.
Wallace, B. A.
Role of the C-terminal domain in the structure and function of tetrameric sodium channels
title Role of the C-terminal domain in the structure and function of tetrameric sodium channels
title_full Role of the C-terminal domain in the structure and function of tetrameric sodium channels
title_fullStr Role of the C-terminal domain in the structure and function of tetrameric sodium channels
title_full_unstemmed Role of the C-terminal domain in the structure and function of tetrameric sodium channels
title_short Role of the C-terminal domain in the structure and function of tetrameric sodium channels
title_sort role of the c-terminal domain in the structure and function of tetrameric sodium channels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791462/
https://www.ncbi.nlm.nih.gov/pubmed/24051986
http://dx.doi.org/10.1038/ncomms3465
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