Abstract
K+ channels conduct and regulate K+ flux across the cell membrane. Several crystal structures and biophysical studies of tetrameric ion channels have revealed many of the structural details of ion selectivity and gating. A narrow pore lined with four arrays of carbonyl groups is responsible for ion selectivity, whereas a conformational change of the four inner transmembrane helices (TM2) is involved in gating. We used NMR to examine full-length KcsA, a prototypical K+ channel, in its open, closed and intermediate states. These studies reveal that at least two conformational states exist both in the selectivity filter and near the C-terminal ends of the TM2 helices. In the ion-conducting open state, we observed rapid structural exchange between two conformations of the filter, presumably of low and high K+ affinity, respectively. Such measurements of millisecond-timescale dynamics reveal the basis for simultaneous ion selection and gating.
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Acknowledgements
This work was supported in part by the US National Institutes of Health (GM74929 and GM56653). R.R. is a Pew Scholar and the Helen McLoraine Development Chair in Neurobiology. K.A.B. would like to thank the American Heart Association for fellowship support.
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K.A.B. and C.T. prepared KcsA; K.A.B., C.T., W.K. and R.R. collected and analyzed NMR data; K.A.B., C.T., S.C. and R.R. contributed to scientific discussions and prepared the manuscript.
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Supplementary Figures 1–6, Supplementary Table 1–3, Supplementary Methods (PDF 4761 kb)
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Baker, K., Tzitzilonis, C., Kwiatkowski, W. et al. Conformational dynamics of the KcsA potassium channel governs gating properties. Nat Struct Mol Biol 14, 1089–1095 (2007). https://doi.org/10.1038/nsmb1311
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DOI: https://doi.org/10.1038/nsmb1311
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