Structural insights into the functional interaction of KChIP1 with Shal-type K(+) channels

Neuron. 2004 Feb 19;41(4):573-86. doi: 10.1016/s0896-6273(04)00045-5.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites / genetics
  • CHO Cells
  • COS Cells
  • Calcium / metabolism
  • Calcium-Binding Proteins / chemistry*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Membrane / chemistry*
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Cricetinae
  • Crystallography, X-Ray
  • Dimerization
  • Kv Channel-Interacting Proteins
  • Membrane Potentials / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed / genetics
  • Phenylalanine / metabolism
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Voltage-Gated*
  • Protein Structure, Secondary / genetics
  • Protein Structure, Tertiary / genetics
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Rats
  • Sequence Homology, Amino Acid
  • Shal Potassium Channels
  • Tryptophan / metabolism

Substances

  • Calcium-Binding Proteins
  • Kcnd1 protein, rat
  • Kcnd2 protein, rat
  • Kcnip1 protein, rat
  • Kv Channel-Interacting Proteins
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Protein Subunits
  • Shal Potassium Channels
  • Phenylalanine
  • Tryptophan
  • Calcium