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The open pore conformation of potassium channels

Nature volume 417, pages 523–526 (2002)Cite this article

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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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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Authors and Affiliations

  1. Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics and Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, New York, 1230 York Avenue, New York, 10021, USA

    Youxing Jiang, Alice Lee, Jiayun Chen, Martine Cadene, Brian T. Chait & Roderick MacKinnon

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  1. Youxing Jiang
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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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