Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel

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.

[1]  E. Campbell,et al.  Voltage Sensor of Kv1.2: Structural Basis of Electromechanical Coupling , 2005, Science.

[2]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[3]  R. MacKinnon.  Potassium channels and the atomic basis of selective ion conduction (Nobel Lecture). , 2004 .

[4]  G. Yellen,et al.  Intracellular gate opening in Shaker K+ channels defined by high-affinity metal bridges , 2004, Nature.

[5]  D. Parcej,et al.  Structural characterisation of neuronal voltage-sensitive K+ channels heterologously expressed in Pichia pastoris. , 2003, Journal of molecular biology.

[6]  F. Ashcroft,et al.  Crystal Structure of the Potassium Channel KirBac1.1 in the Closed State , 2003, Science.

[7]  M. Cadene,et al.  X-ray structure of a voltage-dependent K+ channel , 2003, Nature.

[8]  F. Sesti,et al.  Hyperpolarization moves S4 sensors inward to open MVP, a methanococcal voltage-gated potassium channel , 2003, Nature Neuroscience.

[9]  Youxing Jiang,et al.  Functional analysis of an archaebacterial voltage-dependent K+ channel , 2003, Nature.

[10]  Zhe Lu,et al.  Coupling between Voltage Sensors and Activation Gate in Voltage-gated K+ Channels , 2002, The Journal of general physiology.

[11]  D. Hackos,et al.  Scanning the Intracellular S6 Activation Gate in the Shaker K+ Channel , 2002, The Journal of general physiology.

[12]  Youxing Jiang,et al.  Crystal structure and mechanism of a calcium-gated potassium channel , 2002, Nature.

[13]  Gary Yellen,et al.  Tight Steric Closure at the Intracellular Activation Gate of a Voltage-Gated K+ Channel , 2001, Neuron.

[14]  R. MacKinnon,et al.  Chemistry of ion coordination and hydration revealed by a K+ channel–Fab complex at 2.0 Å resolution , 2001, Nature.

[15]  R. MacKinnon,et al.  Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors , 2001, Nature.

[16]  N. Grigorieff,et al.  Three-dimensional structure of a voltage-gated potassium channel at 2.5 nm resolution. , 2001, Structure.

[17]  W. R. Kobertz,et al.  Hanging gondola structure of the T1 domain in a voltage-gated K(+) channel. , 2000, Biochemistry.

[18]  R. MacKinnon,et al.  Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels. , 2000, Science.

[19]  Yi Liu,et al.  Blocker protection in the pore of a voltage-gated K+ channel and its structural implications , 2000, Nature.

[20]  F Bezanilla,et al.  The voltage sensor in voltage-dependent ion channels. , 2000, Physiological reviews.

[21]  R. MacKinnon,et al.  Structure of a Voltage-Dependent K+ Channel β Subunit , 1999, Cell.

[22]  Y. Fujiyoshi,et al.  Nicotinic acetylcholine receptor at 4.6 A resolution: transverse tunnels in the channel wall. , 1999, Journal of molecular biology.

[23]  G. Yellen,et al.  The moving parts of voltage-gated ion channels , 1998, Quarterly Reviews of Biophysics.

[24]  C. Stevens,et al.  Crystal structure of the tetramerization domain of the Shaker potassium channel , 1998, Nature.

[25]  B. Chait,et al.  The structure of the potassium channel: molecular basis of K+ conduction and selectivity. , 1998, Science.

[26]  G. Yellen,et al.  Gated Access to the Pore of a Voltage-Dependent K+ Channel , 1997, Neuron.

[27]  D. Papazian,et al.  Potassium Channel α and β Subunits Assemble in the Endoplasmic Reticulum* , 1997, The Journal of Biological Chemistry.

[28]  O. Pongs,et al.  Functional characterization of Kv channel beta‐subunits from rat brain. , 1996, The Journal of physiology.

[29]  K. Rhodes,et al.  βSubunits Promote K+ Channel Surface Expression through Effects Early in Biosynthesis , 1996, Neuron.

[30]  K. Rhodes,et al.  Selective Interaction of Voltage-gated K Channel -Subunits with -Subunits (*) , 1996, The Journal of Biological Chemistry.

[31]  O. Pongs,et al.  Kvβ1 Subunit Binding Specific for Shaker-Related Potassium Channel α Subunits , 1996, Neuron.

[32]  Min Li,et al.  NAB Domain Is Essential for the Subunit Assembly of both α–α and α–β Complexes of Shaker-like Potassium Channels , 1996, Neuron.

[33]  J. Ruppersberg.  Ion Channels in Excitable Membranes , 1996 .

[34]  B. Rudy,et al.  Alternative splicing of the human Shaker K+ channel β1 gene and functional expression of the β2 gene product , 1995 .

[35]  B. Ganetzky,et al.  A potassium channel beta subunit related to the aldo-keto reductase superfamily is encoded by the Drosophila hyperkinetic locus. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[36]  K. McCormack,et al.  Shaker K+ channel β subunits belong to an NAD(P)H-dependent oxidoreductase superfamily , 1994, Cell.

[37]  O. Pongs,et al.  Inactivation properties of voltage-gated K+ channels altered by presence of β-subunit , 1994, Nature.

[38]  O. Pongs,et al.  Primary structure of a beta subunit of alpha-dendrotoxin-sensitive K+ channels from bovine brain. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[39]  F J Sigworth,et al.  Voltage gating of ion channels , 1994, Quarterly Reviews of Biophysics.

[40]  R. Aldrich,et al.  Interactions of amino terminal domains of Shaker K channels with a pore blocking site studied with synthetic peptides , 1993, The Journal of general physiology.

[41]  R. Aldrich,et al.  Energetics of Shaker K channels block by inactivation peptides , 1993, The Journal of general physiology.

[42]  J. Dolly,et al.  Oligomeric properties of alpha-dendrotoxin-sensitive potassium ion channels purified from bovine brain. , 1992, Biochemistry.

[43]  K. Sharp,et al.  Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons , 1991, Proteins.

[44]  P. Kraulis.  A program to produce both detailed and schematic plots of protein structures , 1991 .

[45]  T Hoshi,et al.  Biophysical and molecular mechanisms of Shaker potassium channel inactivation , 1990, Science.

[46]  R. Aldrich,et al.  Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB , 1990, Science.

[47]  B. Sakmann,et al.  Molecular basis of functional diversity of voltage‐gated potassium channels in mammalian brain. , 1989, The EMBO journal.

[48]  M. Lazdunski,et al.  Purification and subunit structure of a putative K+-channel protein identified by its binding properties for dendrotoxin I. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[49]  O. Pongs,et al.  Shaker encodes a family of putative potassium channel proteins in the nervous system of Drosophila. , 1988, The EMBO journal.

[50]  Y. Jan,et al.  Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila. , 1987, Science.

[51]  M. Tanouye,et al.  Molecular characterization of Shaker, a Drosophila gene that encodes a potassium channel , 1987, Cell.

[52]  C. Armstrong.  Interaction of Tetraethylammonium Ion Derivatives with the Potassium Channels of Giant Axons , 1971, The Journal of general physiology.

[53]  C. Stevens,et al.  Inward and delayed outward membrane currents in isolated neural somata under voltage clamp , 1971, The Journal of physiology.