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Electron microscopic analysis of KvAP voltage-dependent K+ channels in an open conformation

Nature volume 430, pages 806810 (12 August 2004) | Download Citation

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Abstract

Voltage-dependent ion channels serve as field-effect transistors by opening a gate in response to membrane voltage changes1. The gate's response to voltage is mediated by voltage sensors2, which are arginine-containing structures that must move with respect to the membrane electric field. We have analysed by electron microscopy a voltage-dependent K+ channel from Aeropyrum pernix (KvAP)3. Fab fragments were attached to ‘voltage sensor paddles’ and identified in the electron microscopy map at 10.5 Å resolution. The extracellular surface location of the Fab fragments in the map is consistent with the membrane-depolarized, open conformation of the channel in electrophysiological experiments. Comparison of the map with a crystal structure4 demonstrates that the voltage sensor paddles are ‘up’ (that is, near the channel's extracellular surface) and situated at the protein–lipid interface. This finding supports the hypothesis that in response to changes in voltage the sensors move at the protein–lipid interface5 rather than in a gating pore surrounded by protein6,7.

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Acknowledgements

We thank members of the MacKinnon lab, S. Darst, N. Opalka and D. Stokes for helpful discussions. This work was supported by grants from the NIH to D.N.W. and R.M. R.M is an investigator in the Howard Hughes Medical Institute.

Author information

Affiliations

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

    • Qiu-Xing Jiang
    •  & Roderick MacKinnon
  2. Skirball Institute of Biomolecular Medicine, New York University Medical Center, 540 First Avenue, New York, New York 10016,USA

    • Da-Neng Wang

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Competing interests

The authors declare that they have no competing financial interests.

Corresponding author

Correspondence to Roderick MacKinnon.

Supplementary information

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    Supplementary Figure

    Comparison of class averages with projections from the electron microscopy map at representative orientations.

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https://doi.org/10.1038/nature02735

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