Article | Published:

Structural basis for gating the high-conductance Ca2+-activated K+ channel

Nature volume 541, pages 5257 (05 January 2017) | Download Citation

Abstract

The precise control of an ion channel gate by environmental stimuli is crucial for the fulfilment of its biological role. The gate in Slo1 K+ channels is regulated by two separate stimuli, intracellular Ca2+ concentration and membrane voltage. Slo1 is thus central to understanding the relationship between intracellular Ca2+ and membrane excitability. Here we present the Slo1 structure from Aplysia californica in the absence of Ca2+ and compare it with the Ca2+-bound channel. We show that Ca2+ binding at two unique binding sites per subunit stabilizes an expanded conformation of the Ca2+ sensor gating ring. These conformational changes are propagated from the gating ring to the pore through covalent linkers and through protein interfaces formed between the gating ring and the voltage sensors. The gating ring and the voltage sensors are directly connected through these interfaces, which allow membrane voltage to regulate gating of the pore by influencing the Ca2+ sensors.

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Acknowledgements

We thank Z. Yu and R. Huang at the Howard Hughes Medical Institute Janelia Cryo-EM facility for assistance in data collection; R. W. Aldrich for comments on the manuscript and members of the MacKinnon laboratory for assistance. This work was supported in part by GM43949. R.K.H. is a Howard Hughes Medical Institute postdoctoral fellow of the Helen Hay Whitney Foundation and R.M. is an investigator of the Howard Hughes Medical Institute.

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Affiliations

  1. Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA

    • Richard K. Hite
    • , Xiao Tao
    •  & Roderick MacKinnon

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Contributions

R.K.H. and X.T. performed the experiments. R.K.H., X.T. and R.M. designed the experiments, analysed the results and prepared the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Roderick MacKinnon.

Reviewer Information Nature thanks F. Horrigan, K. Magleby and J. Rubinstein for their contribution to the peer review of this work.

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Videos

  1. 1.

    Conformational changes to aplyisa Slo1 during Ca2+ and Mg2+ binding

    This video shows the binding of Ca2+ and Mg2+ to aplysia Slo1 and the opening of the channel.

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https://doi.org/10.1038/nature20775

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