Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification

Nat Neurosci. 2005 Mar;8(3):279-87. doi: 10.1038/nn1411. Epub 2005 Feb 20.


N- and C-terminal cytoplasmic domains of inwardly rectifying K (Kir) channels control the ion-permeation pathway through diverse interactions with small molecules and protein ligands in the cytoplasm. Two new crystal structures of the cytoplasmic domains of Kir2.1 (Kir2.1(L)) and the G protein-sensitive Kir3.1 (Kir3.1(S)) channels in the absence of PIP(2) show the cytoplasmic ion-permeation pathways occluded by four cytoplasmic loops that form a girdle around the central pore (G-loop). Significant flexibility of the pore-facing G-loop of Kir2.1(L) and Kir3.1(S) suggests a possible role as a diffusion barrier between cytoplasmic and transmembrane pores. Consistent with this, mutations of the G-loop disrupted gating or inward rectification. Structural comparison shows a di-aspartate cluster on the distal end of the cytoplasmic pore of Kir2.1(L) that is important for modulating inward rectification. Taken together, these results suggest the cytoplasmic domains of Kir channels undergo structural changes to modulate gating and inward rectification.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Analysis of Variance
  • Animals
  • Cloning, Molecular / methods
  • Crystallography / methods
  • Dose-Response Relationship, Drug
  • Electric Conductivity
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Protein beta Subunits / genetics
  • GTP-Binding Protein beta Subunits / metabolism
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / genetics
  • Ion Channel Gating / physiology*
  • Macromolecular Substances
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed / physiology
  • Patch-Clamp Techniques / methods
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Potassium / pharmacology
  • Potassium Channels, Inwardly Rectifying / chemistry*
  • Potassium Channels, Inwardly Rectifying / physiology
  • Protein Conformation
  • Protein Structure, Tertiary* / physiology
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Xenopus laevis


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Protein beta Subunits
  • Kir2.1 channel
  • Macromolecular Substances
  • Phosphatidylinositol 4,5-Diphosphate
  • Potassium Channels, Inwardly Rectifying
  • Recombinant Fusion Proteins
  • Potassium