Using protein backbone mutagenesis to dissect the link between ion occupancy and C-type inactivation in K+ channels
Abstract
C-type inactivation is a gating process that takes place at the selectivity filter of K+ channels. C-type inactivation is important in regulating cellular excitability. A defining characteristic of C-type inactivation is a dependence on the permeant ion, but the underlying mechanism is not known. We use protein backbone mutagenesis to alter ion binding at specific sites in the selectivity filter and determine the effect on inactivation. We show that C-type inactivation is linked to ion occupancy at a specific site in the selectivity filter. This study underscores the utility of unnatural mutagenesis for investigating the mechanisms of channel function. Furthermore, permeant ions modulate function in many channel families; therefore, the approaches used in this study are generally applicable.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- October 2013
- DOI:
- 10.1073/pnas.1314356110
- Bibcode:
- 2013PNAS..11017886M