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X-ray structure of a voltage-dependent K+ channel

Abstract

Voltage-dependent K+ channels are members of the family of voltage-dependent cation (K+, Na+ and Ca2+) channels that open and allow ion conduction in response to changes in cell membrane voltage. This form of gating underlies the generation of nerve and muscle action potentials, among other processes. Here we present the structure of KvAP, a voltage-dependent K+ channel from Aeropyrum pernix. We have determined a crystal structure of the full-length channel at a resolution of 3.2 Å, and of the isolated voltage-sensor domain at 1.9 Å, both in complex with monoclonal Fab fragments. The channel contains a central ion-conduction pore surrounded by voltage sensors, which form what we call ‘voltage-sensor paddles’—hydrophobic, cationic, helix–turn–helix structures on the channel's outer perimeter. Flexible hinges suggest that the voltage-sensor paddles move in response to membrane voltage changes, carrying their positive charge across the membrane.

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Acknowledgements

We thank members of the MacKinnon laboratory for assistance at many stages of this project over five years, M. Long for biochemistry at early stages, J. Lee for studies of Ba2+ on cell growth, D. Wang for teaching us to use the electron microscope, F. Weis-Garcia for assistance with monoclonal antibodies, the staff at CHESS A1 and F1 and NSLSX25, O. Andersen and D. Gadsby for manuscript critique, and R. Mohan for graphic work. This work was supported in part by a National Institutes of Health (NIH) grant to R.M., and by the National Center for Research Resources, NIH to B.T.C. V.R. is supported by a National Science Foundation Graduate Student Research Fellowship, and R.M. is an Investigator in the Howard Hughes Medical Institute.

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The authors declare that they have no competing financial interests.

Correspondence to Roderick MacKinnon.

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Further reading

Figure 1: Structure of the KvAP channel.
Figure 2: Stereo view of the KvAP pore and comparison with the KcsA K+ channel.
Figure 3: Architecture of the KvAP channel.
Figure 4: Functional and structural analysis of the isolated voltage-sensor domain.
Figure 5: Structure of the isolated voltage sensor.
Figure 6: The voltage-sensor paddle is conserved.
Figure 7: Effect of Fabs on voltage-sensor conformation.
Figure 8: Hypothesis for gating charge movements.

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