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The open pore conformation of potassium channels

Abstract

Living cells regulate the activity of their ion channels through a process known as gating. To open the pore, protein conformational changes must occur within a channel's membrane-spanning ion pathway. KcsA and MthK, closed and opened K+ channels, respectively, reveal how such gating transitions occur. Pore-lining ‘inner’ helices contain a ‘gating hinge’ that bends by approximately 30°. In a straight conformation four inner helices form a bundle, closing the pore near its intracellular surface. In a bent configuration the inner helices splay open creating a wide (12 Å) entryway. Amino-acid sequence conservation suggests a common structural basis for gating in a wide range of K+ channels, both ligand- and voltage-gated. The open conformation favours high conduction by compressing the membrane field to the selectivity filter, and also permits large organic cations and inactivation peptides to enter the pore from the intracellular solution.

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Figure 1: Structural elements of the K+ channel pore.
Figure 2: Opened and closed states of K+ channels.
Figure 3: Structure-based sequence analysis suggests conserved gating conformations.
Figure 4: The open pore allows entry of large molecules from the intracellular solution.
Figure 5: The membrane electric potential across the pore changes on opening.

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References

  1. del Camino, D., Holmgren, M., Liu, Y. & Yellen, G. Blocker protection in the pore of a voltage-gated K+ channel and its structural implications. Nature 403, 321–325 (2000)

    Article  ADS  CAS  Google Scholar 

  2. Liu, Y., Holmgren, M., Jurman, M. E. & Yellen, G. Gated access to the pore of a voltage-dependent K+ channel. Neuron 19, 175–184 (1997)

    Article  Google Scholar 

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

    Article  ADS  CAS  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)

    Article  ADS  CAS  Google Scholar 

  5. del Camino, D. & Yellen, G. Tight steric closure at the intracellular activation gate of a voltage-gated K+ channel. Neuron 32, 649–656 (2001)

    Article  CAS  Google Scholar 

  6. Cuello, L. G., Romero, J. G., Cortes, D. M. & Perozo, E. pH-dependent gating in the Streptomyces lividans K+ channel. Biochemistry 37, 3229–3236 (1998)

    Article  CAS  Google Scholar 

  7. 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)

    Article  CAS  Google Scholar 

  8. Perozo, E., Cortes, D. M. & Cuello, L. G. Structural rearrangements underlying K+-channel activation gating. Science 285, 73–78 (1999)

    Article  CAS  Google Scholar 

  9. Liu, Y. S., Sompornpisut, P. & Perozo, E. Structure of the KcsA channel intracellular gate in the open state. Nature Struct. Biol. 8, 883–887 (2001)

    Article  CAS  Google Scholar 

  10. Zhou, M., Morais-Cabral, J. H., Mann, S. & MacKinnon, R. Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors. Nature 411, 657–661 (2001)

    Article  ADS  CAS  Google Scholar 

  11. Jiang, Y. et al. Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417, 515–522 (2002)

    Article  ADS  CAS  Google Scholar 

  12. Flynn, G. E., Johnson, J. P. Jr & Zagotta, W. N. Cyclic nucleotide-gated channels: shedding light on the opening of a channel pore. Nature Rev. Neurosci. 2, 643–651 (2001)

    Article  CAS  Google Scholar 

  13. Sigworth, F. J. Voltage gating of ion channels. Q. Rev. Biophys. 27, 1–40 (1994)

    Article  CAS  Google Scholar 

  14. Bezanilla, F. The voltage sensor in voltage-dependent ion channels. Physiol. Rev. 80, 555–592 (2000)

    Article  CAS  Google Scholar 

  15. Jiang, Y., Pico, A., Cadene, M., Chait, B. T. & MacKinnon, R. Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel. Neuron 29, 593–601 (2001)

    Article  CAS  Google Scholar 

  16. Armstrong, C. M. Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. J. Gen. Physiol. 58, 413–437 (1971)

    Article  CAS  Google Scholar 

  17. Armstrong, C. M. Ionic pores, gates, and gating currents. Q. Rev. Biophys. 7, 179–210 (1974)

    Article  CAS  Google Scholar 

  18. Holmgren, M., Smith, P. L. & Yellen, G. Trapping of organic blockers by closing of voltage-dependent K+ channels: evidence for a trap door mechanism of activation gating. J. Gen. Physiol. 109, 527–535 (1997)

    Article  CAS  Google Scholar 

  19. Mitcheson, J. S., Chen, J., Lin, M., Culberson, C. & Sanguinetti, M. C. A structural basis for drug-induced long QT syndrome. Proc. Natl Acad. Sci. USA 97, 12329–12333 (2000)

    Article  ADS  CAS  Google Scholar 

  20. Roux, B. & MacKinnon, R. The cavity and pore helices in the KcsA K+ channel: electrostatic stabilization of monovalent cations. Science 285, 100–102 (1999)

    Article  CAS  Google Scholar 

  21. Hoshi, T., Zagotta, W. N. & Aldrich, R. W. Biophysical and molecular mechanisms of Shaker potassium channel inactivation. Science 250, 533–538 (1990)

    Article  ADS  CAS  Google Scholar 

  22. Zagotta, W. N., Hoshi, T. & Aldrich, R. W. Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB. Science 250, 568–571 (1990)

    Article  ADS  CAS  Google Scholar 

  23. Bezanilla, F. & Armstrong, C. M. Inactivation of the sodium channel. I. Sodium current experiments. J. Gen. Physiol. 70, 549–566 (1977)

    Article  CAS  Google Scholar 

  24. Armstrong, C. M. & Bezanilla, F. Inactivation of the sodium channel. II. Gating current experiments. J. Gen. Physiol. 70, 567–590 (1977)

    Article  CAS  Google Scholar 

  25. Rettig, J. et al. Inactivation properties of voltage-gated K+ channels altered by presence of β-subunit. Nature 369, 289–294 (1994)

    Article  ADS  CAS  Google Scholar 

  26. Warwicker, J. & Watson, H. C. Calculation of the electric potential in the active site cleft due to alpha-helix dipoles. J. Mol. Biol. 157, 671–679 (1982)

    Article  CAS  Google Scholar 

  27. Klapper, I., Hagstrom, R., Fine, R., Sharp, K. & Honig, B. Focusing of electric fields in the active site of Cu-Zn superoxide dismutase: effects of ionic strength and amino-acid modification. Proteins 1, 47–59 (1986)

    Article  CAS  Google Scholar 

  28. Carson, M. Ribbons. Methods Enzymol. 277, 493–505 (1997)

    Article  CAS  Google Scholar 

  29. Esnouf, R. M. An extensively modified version of MolScript that includes greatly enhanced coloring capabilities. J. Mol. Graph. Model. 15, 132–133 (1997)

    Article  CAS  Google Scholar 

  30. Nicholls, A., Sharp, K. A. & Honig, B. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 11, 281–296 (1991)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the staff at the National Synchrotron Light Source, Brookhaven National Laboratory, X-25, the Cornell High Energy Synchrotron Source, F1, and the Advanced Light Source, Lawrence Berkeley Laboratory, 5.0.2 for synchrotron support; members of the MacKinnon laboratory for assistance; R. Dutzler and R. Xie for programming and graphical assistance; F. Sigworth, P. Jordan, C. Miller and D. Gadsby for discussions; and W. Chin for help in manuscript preparation. This work was supported by grants from the NIH to R.M. and from the National Center for Research Resources, NIH, to B.T.C. R.M. is an investigator in the Howard Hughes Medical Institute.

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Correspondence to Roderick MacKinnon.

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Jiang, Y., Lee, A., Chen, J. et al. The open pore conformation of potassium channels. Nature 417, 523–526 (2002). https://doi.org/10.1038/417523a

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