Abstract
Potassium channels allow K+ ions to diffuse through their pores while preventing smaller Na+ ions from permeating. Discrimination between these similar, abundant ions enables these proteins to control electrical and chemical activity in all organisms. Selection occurs at the narrow selectivity filter containing structurally identified K+ binding sites. Selectivity is thought to arise because smaller ions such as Na+ do not bind to these K+ sites in a thermodynamically favorable way. Using the model K+ channel KcsA, we examined how intracellular Na+ and Li+ interact with the pore and the permeant ions using electrophysiology, molecular dynamics simulations and X-ray crystallography. Our results suggest that these small cations have a separate binding site within the K+ selectivity filter. We propose that selective permeation from the intracellular side primarily results from a large energy barrier blocking filter entry for Na+ and Li+ in the presence of K+, not from a difference of binding affinity between ions.
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Acknowledgements
The authors would like to thank D. Posson, J. McCoy, D. Kim, A. George and L. DeFelice for insightful discussions and acknowledge support from American Heart Association grant 0630168ZN and National Institutes of Health grant GM077560 to C.M.N. A.N.T. is funded by a National Science Foundation Graduate Research Fellowships Program grant. T.W.A. and I.K. would like to thank S. Noskov for providing and testing Li+ parameters and acknowledge support from a National Science Foundation CAREER award MCB-0546768. T.D.P. acknowledges support from National Institutes of Health grants 1-T32-NS07491-06 and 5-T32-GM008320-19. T.M.I. acknowledges support from National Institutes of Health grant 5-R01-GM079419-03. Use of the Advanced Photon Source at Argonne National Laboratory was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract no. DE-AC02-06CH11357. Use of the Life Sciences Collaborative Access Team Sector 21 beamline was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor for the support of this research program (Grant 085P1000817).
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A.N.T., I.K., T.D.P., T.M.I., T.W.A. and C.M.N. performed research, analyzed data and wrote the paper.
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Thompson, A., Kim, I., Panosian, T. et al. Mechanism of potassium-channel selectivity revealed by Na+ and Li+ binding sites within the KcsA pore. Nat Struct Mol Biol 16, 1317–1324 (2009). https://doi.org/10.1038/nsmb.1703
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DOI: https://doi.org/10.1038/nsmb.1703
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