Abstract
Four Kv channel-interacting proteins (KChIP1 through KChIP4) interact directly with the N-terminal domain of three Shal-type voltage-gated potassium channels (Kv4.1, Kv4.2, and Kv4.3) to modulate cell surface expression and function of Kv4 channels. Here we report a 2.0 Angstrom crystal structure of the core domain of KChIP1 (KChIP1*) in complex with the N-terminal fragment of Kv4.2 (Kv4.2N30). The complex reveals a clam-shaped dimeric assembly. Four EF-hands from each KChIP1 form each shell of the clam. The N-terminal end of Kv4.2 forming an alpha helix (alpha1) and the C-terminal alpha helix (H10) of KChIP1 are enclosed nearly coaxially by these shells. As a result, the H10 of KChIP1 and alpha1 of Kv4.2 mediate interactions between these two molecules, structurally reminiscent of the interactions between calmodulin and its target peptides. Site-specific mutagenesis combined with functional characterization shows that those interactions mediated by alpha1 and H10 are essential to the modulation of Kv4.2 by KChIPs.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Binding Sites / genetics
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CHO Cells
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COS Cells
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Calcium / metabolism
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Calcium-Binding Proteins / chemistry*
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism
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Cell Membrane / chemistry*
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Cell Membrane / genetics
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Cell Membrane / metabolism
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Cricetinae
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Crystallography, X-Ray
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Dimerization
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Kv Channel-Interacting Proteins
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Membrane Potentials / genetics
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed / genetics
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Phenylalanine / metabolism
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Potassium Channels / chemistry*
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Potassium Channels / genetics
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Potassium Channels / metabolism
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Potassium Channels, Voltage-Gated*
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Protein Structure, Secondary / genetics
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Protein Structure, Tertiary / genetics
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Protein Subunits / chemistry
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Rats
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Sequence Homology, Amino Acid
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Shal Potassium Channels
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Tryptophan / metabolism
Substances
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Calcium-Binding Proteins
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Kcnd1 protein, rat
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Kcnd2 protein, rat
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Kcnip1 protein, rat
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Kv Channel-Interacting Proteins
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Potassium Channels
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Potassium Channels, Voltage-Gated
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Protein Subunits
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Shal Potassium Channels
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Phenylalanine
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Tryptophan
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Calcium