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Small vertical movement of a K+ channel voltage sensor measured with luminescence energy transfer

Abstract

Voltage-gated ion channels open and close in response to voltage changes across electrically excitable cell membranes1. Voltage-gated potassium (Kv) channels are homotetramers with each subunit constructed from six transmembrane segments, S1–S6 (ref. 2). The voltage-sensing domain (segments S1–S4) contains charged arginine residues on S4 that move across the membrane electric field2,3, modulating channel open probability. Understanding the physical movements of this voltage sensor is of fundamental importance and is the subject of controversy. Recently, the crystal structure of the KvAP4 channel motivated an unconventional ‘paddle model’ of S4 charge movement, indicating that the segments S3b and S4 might move as a unit through the lipid bilayer with a large (15–20-Å) transmembrane displacement5. Here we show that the voltage-sensor segments do not undergo significant transmembrane translation. We tested the movement of these segments in functional Shaker K+ channels by using luminescence resonance energy transfer to measure distances between the voltage sensors and a pore-bound scorpion toxin. Our results are consistent with a 2-Å vertical displacement of S4, not the large excursion predicted by the paddle model. This small movement supports an alternative model in which the protein shapes the electric field profile, focusing it across a narrow region of S4 (ref. 6).

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Figure 1: Diagram of the paddle model.
Figure 2: LRET raw data and distance calculations.
Figure 3: A model of Shaker with docked AgTX predicts four distances for each LRET experiment.
Figure 4: Average distances for many Shaker sites.

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Acknowledgements

We thank B. Roux for putting together coordinates for a combined model of the AgTX–Shaker complex23 with the model for the Shaker open state21, and L. Kolmakova-Partensky and T. Lawrecki for technical assistance. This work was supported by grants from the NIH, NSF, the Carver Foundation and the Cottrell funds of the Research Corp to P.R.S., from an NIH grant to F.P., and from the Howard Hughes Medical Institute to C.M. P.R.S. also thanks J. Ackland, J. Stenehjem and the other members of the Sharp Rehabilitation Center of San Diego for their care, which made this study possible.

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Correspondence to Paul R. Selvin.

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Posson, D., Ge, P., Miller, C. et al. Small vertical movement of a K+ channel voltage sensor measured with luminescence energy transfer. Nature 436, 848–851 (2005). https://doi.org/10.1038/nature03819

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