Structure of the C-terminal domain of the Prokaryotic Sodium Channel Orthologue NsvBa
Miller, Wayne and Miles, Andrew J. and Wallace, Bonnie (2016) Structure of the C-terminal domain of the Prokaryotic Sodium Channel Orthologue NsvBa. European Biophysics Journal with Biophysics letters 45 (8), pp. 807-814. ISSN 0175-7571.
Crystallographic and electrophysiological studies have recently provided insight into the structure, function and drug binding of prokaryotic sodium channels. These channels exhibit significant sequence identities, especially in their transmembrane regions, with human voltage-gated sodium channels. However, rather than being single polypeptides with four homologous domains, they are tetramers of single domain polypeptides, with a C-terminal domain (CTD) composed of an inter-subunit four helix coiled-coil. The structures of the CTDs differ between orthologues. In NavBh and NavMs, the C-termini form a disordered region adjacent to the final transmembrane helix, followed by a coiled-coil region, as demonstrated by synchrotron radiation circular dichroism (SRCD) and double electron-electron resonance electron paramagnetic resonance spectroscopic measurements. In contrast, in the crystal structure of the NavAe orthologue, the entire C-terminus is comprised of a helical region followed by a coiled-coil. In this study we have examined the CTD of the NsvBa from Bacillus alcalophilus, which unlike other orthologues is predicted by different methods to have different types of structures: either a disordered adjacent to the transmembrane region, followed by a helical coiled-coil, or a fully helical CTD. To discriminate between the two possible structures we have used SRCD spectroscopy to experimentally determine the secondary structure of the C-terminus of this orthologue and used the results as the basis for modelling the transition between open and closed conformations of the channel.
|Additional Information:||The final publication is available at Springer via the link above.|
|Keyword(s) / Subject(s):||Voltage-gated sodium channels, synchrotron radiation circular dichroism spectroscopy, structure prediction, bioinformatics, coiled-coil|
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Research Centre:||Bioinformatics, Bloomsbury Centre for, Structural Molecular Biology, Institute of (ISMB)|
|Date Deposited:||29 Apr 2016 13:50|
|Last Modified:||23 Apr 2017 01:05|
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