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Crystal structure and mechanism of a calcium-gated potassium channel

Nature volume 417, pages 515–522 (2002)Cite this article

Abstract

Ion channels exhibit two essential biophysical properties; that is, selective ion conduction, and the ability to gate-open in response to an appropriate stimulus. Two general categories of ion channel gating are defined by the initiating stimulus: ligand binding (neurotransmitter- or second-messenger-gated channels) or membrane voltage (voltage-gated channels). Here we present the structural basis of ligand gating in a K+ channel that opens in response to intracellular Ca2+. We have cloned, expressed, analysed electrical properties, and determined the crystal structure of a K+ channel (MthK) from Methanobacterium thermoautotrophicum in the Ca2+-bound, opened state. Eight RCK domains (regulators of K+ conductance) form a gating ring at the intracellular membrane surface. The gating ring uses the free energy of Ca2+ binding in a simple manner to perform mechanical work to open the pore.

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Figure 1: Ligand-activated ion channel gating.
Figure 2: Sequence analysis of proteins containing RCK domains.
Figure 3: Biochemical analysis of MthK.
Figure 4: Electrophysiological analysis of MthK in lipid bilayers.
Figure 5: Structure of the MthK K+ channel.
Figure 6: Structure of the gating ring.
Figure 7: Comparison of different RCK domains reveals possible gating motions.
Figure 8: Proposed mechanism of gating.

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Acknowledgements

We thank the staff at the NSLS, Brookhaven National Laboratory, X-25, Cornell High Energy Synchrotron Source, F1 and ALS, Lawrence Berkeley Laboratory, 5.0.2 for synchrotron support; members of the MacKinnon laboratory, P. Model and M. Russel for discussion; C. Miller and D. Gadsby for critical reading of the manuscript; and W. Chin for help in manuscript preparation. This work was supported by grants from the NIH to R.M. and the National Centre for Research Resources, NIH, to B.T.C. R.M. is an investigator in the Howard Hughes Medical Institute.

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  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. Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417, 515–522 (2002). https://doi.org/10.1038/417515a

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