Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel
Abstract
Voltage-dependent potassium ion (K+) channels (Kv channels) conduct K+ ions across the cell membrane in response to changes in the membrane voltage, thereby regulating neuronal excitability by modulating the shape and frequency of action potentials. Here we report the crystal structure, at a resolution of 2.9 angstroms, of a mammalian Kv channel, Kv1.2, which is a member of the Shaker K+ channel family. This structure is in complex with an oxido-reductase β subunit of the kind that can regulate mammalian Kv channels in their native cell environment. The activation gate of the pore is open. Large side portals communicate between the pore and the cytoplasm. Electrostatic properties of the side portals and positions of the T1 domain and β subunit are consistent with electrophysiological studies of inactivation gating and with the possibility of K+ channel regulation by the β subunit.
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We thank A. Lee, V. Ruta, and members of the MacKinnon laboratory for helpful discussions; R. Jain for initial experiments with lipids; Q. Wang and B. T. Chait for mass spectrometry; R. Dutzler for assistance with data collection; O. Pongs for Kv1.2 DNA; J. Trimmer for β2 subunit DNA; Brookhaven National Laboratory (National Synchrotron Light Source beamlines X25 and X29) and the Swiss Light Source (beamline PX1) staff for assistance in data collection; and W. Chin for help with manuscript preparation. This work was supported in part by NIH grant no. GM43949 to R.M. and NIH grant no. RR00862 to B. T. Chait. R.M. is an Investigator in the Howard Hughes Medical Institute. Atomic coordinates and structure factors have been deposited with the Protein Data Bank with accession ID 2A79.
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Science
Volume 309 | Issue 5736
5 August 2005
5 August 2005
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American Association for the Advancement of Science.
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Received: 17 June 2005
Accepted: 5 July 2005
Published in print: 5 August 2005
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