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Energetic optimization of ion conduction rate by the K+ selectivity filter

Abstract

The K+ selectivity filter catalyses the dehydration, transfer and rehydration of a K+ ion in about ten nanoseconds. This physical process is central to the production of electrical signals in biology. Here we show how nearly diffusion-limited rates are achieved, by analysing ion conduction and the corresponding crystallographic ion distribution in the selectivity filter of the KcsA K+ channel. Measurements with K+ and its slightly larger analogue, Rb+, lead us to conclude that the selectivity filter usually contains two K+ ions separated by one water molecule. The two ions move in a concerted fashion between two configurations, K+-water-K+-water (1,3 configuration) and water-K+-water-K+ (2,4 configuration), until a third ion enters, displacing the ion on the opposite side of the queue. For K+, the energy difference between the 1,3 and 2,4 configurations is close to zero, the condition of maximum conduction rate. The energetic balance between these configurations is a clear example of evolutionary optimization of protein function.

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Figure 1: Binding sites for K+ ions in the KcsA K+ channel.
Figure 2: Rubidium conduction and crystallographic distribution of Rb+ ions in the selectivity filter.
Figure 3: Potassium conduction and crystallographic distribution of K+ ions in the selectivity filter.
Figure 4: Analysis of a conduction-state diagram constructed on the basis of the electron density profiles.
Figure 5: The biologically important throughput cycle for K+ ions.
Figure 6: Energetic optimization of K+ ion conduction.

References

  1. Doyle, D. A. et al. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280, 69–77 (1998).

    ADS  CAS  Article  Google Scholar 

  2. Eisenman, G., Latorre, R. & Miller, C. Multi-ion conduction and selectivity in the high-conductance Ca++-activated K+ channel from skeletal muscle. Biophys. J. 50, 1025–1034 (1986).

    ADS  CAS  Article  Google Scholar 

  3. LeMasurier, M., Heginbotham, L. & Miller, C. KcsA: It's a potassium channel. J. Gen. Physiol. 118, 303–314 (2001).

    CAS  Article  Google Scholar 

  4. Zhou, Y., Morais-Cabral, J. H., Kaufman, A. & MacKinnon, R. Chemistry of ion coordination and hydration revealed by a K+ channel–Fab complex at 2.0 Å resolution. Nature 414, 43–48 (2001).

    ADS  CAS  Article  Google Scholar 

  5. Dunitz, J. D. & Dobler, M. in Biological Aspects of Inorganic Chemistry (eds Addison, A. W., Cullen, W. R., Dolphin, D. & James, B. R.) 113–140 (Wiley, New York, 1977).

    Google Scholar 

  6. Dobler, v. M., Dunitz, J. D. & Kilbourn, B. T. Die struktur des KNCS-Komplexes von nonactin. Helv. Chim. Acta 52, 2573–2583 (1969).

    CAS  Article  Google Scholar 

  7. Neupert-Laves, K. & Dobler, M. The crystal structure of a K+ complex of valinomycin. Helv. Chim. Acta 58, 432–442 (1975).

    CAS  Article  Google Scholar 

  8. Hodgkin, A. L. & Keynes, R. D. The potassium permeability of a giant nerve fibre. J. Physiol. (Lond.) 128, 61–88 (1955).

    CAS  Article  Google Scholar 

  9. Begenisich, T. & De Weer, P. Potassium flux ratio in voltage-clamped squid giant axons. J. Gen. Physiol. 76, 83–98 (1980).

    CAS  Article  Google Scholar 

  10. Bestergaard-Bogind, B., Stampe, P. & Christophersen, P. Single-file diffusion through the Ca2+-activated K+ channel of human red cells. J. Membr. Biol. 88, 67–75 (1985).

    Article  Google Scholar 

  11. Neyton, J. & Miller, C. Potassium blocks barium permeation through a calcium-activated potassium channel. J. Gen. Physiol. 92, 549–567 (1988).

    CAS  Article  Google Scholar 

  12. Neyton, J. & Miller, C. Discrete Ba2+ block as a probe of ion occupancy and pore structure in the high-conductance Ca2+-activated K+ channel. J. Gen. Physiol. 92, 569–586 (1988).

    CAS  Article  Google Scholar 

  13. Alcayaga, C., Cecchi, X., Alvarez, O. & Latorre, R. Streaming potential measurements in Ca2+-activated K+ channels from skeletal and smooth muscle. Biophys. J. 55, 367–371 (1989).

    CAS  Article  Google Scholar 

  14. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307–326 (1997).

    CAS  Article  Google Scholar 

  15. Collaborative Computational Project, No. 4. The CCP4 Suite: Programs for X-ray crystallography. Acta Crystallogr. D 50, 760–763 (1994).

    Article  Google Scholar 

  16. Gamblin, S. J., Rodgers, D. W. & Stehle, T. Proc. CCP4 Study Weekend 163–169 (Daresbury Laboratory, Daresbury, 1996).

    Google Scholar 

  17. Brunger, A. T. et al. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D 54, 905–921 (1998).

    CAS  Article  Google Scholar 

  18. Kleywegt, G. J. & Jones, T. A. in From the First Map to Final Model. Proc. CCP4 Study Weekend (eds Bailey, S., Hubbard, R. & Waller, D.) 59–66 (Daresbury Laboratory, Daresbury, 1994).

    Google Scholar 

  19. Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjeldgaard, M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47, 110–119 (1991).

    Article  Google Scholar 

  20. Kleywegt, G. J. & Jones, T. A. xdlMAPMAN and xdlDATAMAN—Programs for reformatting, analysis and manipulation of biomacromolecular electron-density maps and reflection data sets. Acta Crystallogr. D 52, 826–828 (1996).

    CAS  Article  Google Scholar 

  21. Heginbotham, L., LeMasurier, M., Kolmakova-Partensky, L. & Miller, C. Single streptomyces lividans K+ channels. Functional asymmetries and sidedness of proton activation. J. Gen. Physiol. 114, 551–560 (1999).

    CAS  Article  Google Scholar 

  22. Heginbotham, L., Kolmakova-Partensky, L. & Miller, C. Functional reconstitution of a prokaryotic K+ channel. J. Gen. Physiol. 111, 741–749 (1998).

    CAS  Article  Google Scholar 

  23. Cuello, L. G., Romero, J. G., Cortes, D. M. & Perozo, E. pH-dependent gating in the Streptomyces lividans K+ channel. Biochemistry 37, 3229–3236 (1988).

    Article  Google Scholar 

  24. Koonin, S. E. Computational Physics (Benjamin/Cummings, Menlo Park, 1986).

    Google Scholar 

  25. Kramers, H. A. Brownian motion in a field of force and the diffusion model of chemical reactions. Physica 7, 284–304 (1940).

    ADS  MathSciNet  CAS  Article  Google Scholar 

  26. Kraulis, P. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  27. Bacon, D. & Anderson, W. F. A fast algorithm for rendering space filling molecule pictures. J. Mol. Graph 6, 219–220 (1988).

    Article  Google Scholar 

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Acknowledgements

We thank, for assistance, the staff at the National Synchrotron Light Source X-25; at Cornell High Energy Synchrotron Source, A1 and F1; at the Advanced Photon Source, ID19; and at the European Synchrotron Radiation Source, ID13. We thank Y. Jiang, R. Dutzler and A. Pico for assistance in data collection; B. Roux for discussions; and F. Valiyaveetil for discussion and advice on the manuscript. This work was supported by a grant from the National Institutes of Health to R.M. R.M. is an investigator in the Howard Hughes Medical Institute.

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Morais-Cabral, J., Zhou, Y. & MacKinnon, R. Energetic optimization of ion conduction rate by the K+ selectivity filter. Nature 414, 37–42 (2001). https://doi.org/10.1038/35102000

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