Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits

Nat Neurosci. 2007 Jan;10(1):32-9. doi: 10.1038/nn1822. Epub 2006 Dec 24.


KChIPs coassemble with pore-forming Kv4 alpha subunits to form a native complex in the brain and heart and regulate the expression and gating properties of Kv4 K(+) channels, but the mechanisms underlying these processes are unknown. Here we report a co-crystal structure of the complex of human Kv4.3 N-terminus and KChIP1 at a 3.2-A resolution. The structure reveals a unique clamping action of the complex, in which a single KChIP1 molecule, as a monomer, laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner, forming an octamer. The proximal N-terminal peptide of Kv4.3 is sequestered by its binding to an elongated groove on the surface of KChIP1, which is indispensable for the modulation of Kv4.3 by KChIP1, and the same KChIP1 molecule binds to an adjacent T1 domain to stabilize the tetrameric Kv4.3 channels. Taken together with biochemical and functional data, our findings provide a structural basis for the modulation of Kv4 by KChIPs.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Glycine / metabolism
  • Humans
  • Ion Channel Gating
  • Kv Channel-Interacting Proteins / chemistry
  • Kv Channel-Interacting Proteins / genetics
  • Kv Channel-Interacting Proteins / metabolism*
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Oocytes
  • Patch-Clamp Techniques / methods
  • Proline / metabolism
  • Protein Structure, Tertiary / genetics
  • Protein Subunits / physiology
  • Shal Potassium Channels / chemistry
  • Shal Potassium Channels / genetics
  • Shal Potassium Channels / metabolism*
  • Transfection
  • Xenopus laevis


  • Kv Channel-Interacting Proteins
  • Protein Subunits
  • Shal Potassium Channels
  • Proline
  • Glycine

Associated data

  • PDB/2NZ0