O’Reilly, A.O. and Lattrell, A. and Miles, Andrew J. and Klinger, A.B. and Nau, C. and Wallace, Bonnie A. and Lampert, A. (2017) Mutagenesis of the NaChBac sodium channel discloses a functional role for a conserved S6 asparagine. European Biophysics Journal 46 (7), pp. 665-674. ISSN 0175-7571.
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Abstract
Asparagine is conserved in the S6 transmembrane segments of all voltage-gated sodium, calcium, and TRP channels identified to date. A broad spectrum of channelopathies including cardiac arrhythmias, epilepsy, muscle diseases, and pain disorders is associated with its mutation. To investigate its effects on sodium channel functional properties, we mutated the simple prokaryotic sodium channel NaChBac. Electrophysiological characterization of the N225D mutant reveals that this conservative substitution shifts the voltage-dependence of inactivation by 25 mV to more hyperpolarized potentials. The mutant also displays greater thermostability, as determined by synchrotron radiation circular dichroism spectroscopy studies of purified channels. Based on our analyses of high-resolution structures of NaChBac homologues, we suggest that the side-chain amine group of asparagine 225 forms one or more hydrogen bonds with different channel elements and that these interactions are important for normal channel function. The N225D mutation eliminates these hydrogen bonds and the structural consequences involve an enhanced channel inactivation.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | Ion channel inactivation, Whole-cell patch clamp, Molecular modeling, Circular dichroism spectroscopy, Thermal stability |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Depositing User: | Administrator |
| Date Deposited: | 12 Jan 2018 10:10 |
| Last Modified: | 02 Aug 2023 17:35 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/19602 |
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