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Novel insights into K+ selectivity from high-resolution structures of an open K+ channel pore

Abstract

K+ channels are highly selective for K+ over Na+. Here we present several crystal structures of the MthK K+ channel pore at up to 1.45-Å resolution. The MthK selectivity filter maintains a conductive conformation even in the absence of K+, allowing the channel to conduct Na+. The high-resolution structures, along with single-channel recordings, allow for an accurate analysis of how K+ competes with Na+ in a conductive selectivity filter. At high K+ concentrations, two K+ ions equivalently occupy the four sites in the selectivity filter, whereas at low K+/high Na+ concentrations, a single K+ ion remains bound in the selectivity filter, preferably at site 1 or site 3. This single K+ binding at low concentration effectively blocks the permeation of Na+, providing a structural basis for the anomalous mole-fraction effect, a key property of multi-ion pores.

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Figure 1: Structure of open MthK pore in complex with K+ (in 100 mM K+).
Figure 2: The selectivity filter of MthK maintains a conductive conformation in low-K+ or Na+-only environments.
Figure 3: K+ binding in the selectivity filter at high and low concentrations.

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Acknowledgements

We thank A. Alam for discussion and critical review of the manuscript. Use of the Argonne National Laboratory Structural Biology Center beamlines at the Advanced Photon Source was supported by the US Department of Energy, Office of Energy Research. We thank the beamline staff for assistance in data collection. This work was supported by the Howard Hughes Medical Institute and by grants from the US National Institutes of Health, National Institute of General Medical Science (RO1 GM071621), the David and Lucile Packard Foundation and the Welch Foundation.

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S.Y. determined the structures; Y.L. performed the electrophysiological analysis; S.Y., Y.L. and Y.J. designed the research, analyzed data and wrote the manuscript.

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Correspondence to Sheng Ye or Youxing Jiang.

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The authors declare no competing financial interests.

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Supplementary Figures 1 and 2 and Supplementary Table 1 (PDF 127 kb)

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Ye, S., Li, Y. & Jiang, Y. Novel insights into K+ selectivity from high-resolution structures of an open K+ channel pore. Nat Struct Mol Biol 17, 1019–1023 (2010). https://doi.org/10.1038/nsmb.1865

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