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Spectroscopic mapping of voltage sensor movement in the Shaker potassium channel

Nature volume 402, pages 813817 (16 December 1999) | Download Citation

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Abstract

Voltage-gated ion channels underlie the generation of action potentials and trigger neurosecretion and muscle contraction. These channels consist of an inner pore-forming domain, which contains the ion permeation pathway and elements of its gates, together with four voltage-sensing domains, which regulate the gates1,2,3,4,5,6. To understand the mechanism of voltage sensing it is necessary to define the structure and motion of the S4 segment, the portion of each voltage-sensing domain that moves charged residues across the membrane in response to voltage change7,8,9,10,11,12,13,14. We have addressed this problem by using fluorescence resonance energy transfer as a spectroscopic ruler15,16,17 to determine distances between S4s in the Shaker K+ channel in different gating states. Here we provide evidence consistent with S4 being a tilted helix that twists during activation. We propose that helical twist contributes to the movement of charged side chains across the membrane electric field and that it is involved in coupling voltage sensing to gating.

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Acknowledgements

We thank L. Llewelyn for making the linked dimers, and A. Glazer, H. Lecar, J. Ngai, E. Loots, O. Baker, H. P. Larsson, M. Moronne and all the other members of the laboratory for helpful discussions. This work was supported by grants from NIH, American Heart Foundation, CA Affiliate, Department of Energy and Lawrence Berkeley National Laboratory Physical Bioscience Division.

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  1. Department of Molecular & Cell Biology, University of California, Berkeley, 271 Life Science Addition, Berkeley, California 94720-3200, USA

    • K. S. Glauner
    • , L. M. Mannuzzu
    • , C. S. Gandhi
    •  & E. Y. Isacoff

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Correspondence to E. Y. Isacoff.

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https://doi.org/10.1038/45561

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