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Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment

Nature volume 450, pages 376–382 (2007)Cite this article

Abstract

Voltage-dependent K+ (Kv) channels repolarize the action potential in neurons and muscle. This type of channel is gated directly by membrane voltage through protein domains known as voltage sensors, which are molecular voltmeters that read the membrane voltage and regulate the pore. Here we describe the structure of a chimaeric voltage-dependent K+ channel, which we call the ‘paddle-chimaera channel’, in which the voltage-sensor paddle has been transferred from Kv2.1 to Kv1.2. Crystallized in complex with lipids, the complete structure at 2.4 ångström resolution reveals the pore and voltage sensors embedded in a membrane-like arrangement of lipid molecules. The detailed structure, which can be compared directly to a large body of functional data, explains charge stabilization within the membrane and suggests a mechanism for voltage-sensor movements and pore gating.

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Figure 1: Paddle-chimaera channel.
Figure 2: Comparison of the paddle-chimeara channel with other K + channel structures.
Figure 3: Lipids in the structure.
Figure 4: Details of the voltage sensor.
Figure 5: Mapping of biochemical data on the voltage sensor.
Figure 6: Hypothetical mechanism of voltage-dependent gating.

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Acknowledgements

We thank A. L. MacKinnon for CTX and discussions, S.-Y. Lee and T. Muir for discussions, K. Swartz for providing information enabling the chimaera construction, and the staff at beamline X29, NSLS, Brookhaven National Laboratory. R.M. is an Investigator in the Howard Hughes Medical Institute. This work was supported by the NIH (R.M.).

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  1. Stephen B. Long

    Present address: Present address: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, Box 414, 1275 York Avenue, New York, New York 10065, USA.,

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  1. Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA ,

    Stephen B. Long, Xiao Tao, Ernest B. Campbell & Roderick MacKinnon

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The file contains Supplementary Figures 1-2 with Legends and Supplementary Table 1 with X-ray data collection and refinement statistics. (PDF 3213 kb)

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Long, S., Tao, X., Campbell, E. et al. Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment. Nature 450, 376–382 (2007). https://doi.org/10.1038/nature06265

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