Glycine 30 in iberiotoxin is a critical determinant of its specificity for maxi-K versus K(V) channels

FEBS Lett. 2002 Sep 11;527(1-3):298-302. doi: 10.1016/s0014-5793(02)03256-8.


Iberiotoxin (IbTX) is a remarkably selective alpha-K toxin peptide (alpha-KTx) inhibitor of the maxi-K channel. In contrast, the highly homologous charybdotoxin inhibits both the maxi-K and K(V)1.3 channels with similar high affinity. The present study investigates the molecular basis for this specificity through mutagenesis of IbTX. The interactions of mutated peptides with maxi-K and K(V)1.3 channels were monitored through dose-dependent displacement of specifically bound iodinated alpha-KTx peptides from membranes expressing these channels. Results of these studies suggest that the presence of a glycine at position 30 in IbTX is a major determinant of its specificity while the presence of four unique acidic residues in IbTX is not.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Asparagine
  • Cells, Cultured
  • Glycine / chemistry*
  • Humans
  • Kv1.3 Potassium Channel
  • Large-Conductance Calcium-Activated Potassium Channels
  • Molecular Sequence Data
  • Mutation
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism*
  • Potassium Channels / metabolism*
  • Potassium Channels, Calcium-Activated / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Protein Conformation
  • Scorpion Venoms / genetics
  • Scorpion Venoms / metabolism
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Toxins, Biological / metabolism*


  • KCNA3 protein, human
  • Kv1.3 Potassium Channel
  • Large-Conductance Calcium-Activated Potassium Channels
  • Peptides
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Potassium Channels, Voltage-Gated
  • Scorpion Venoms
  • Toxins, Biological
  • Asparagine
  • iberiotoxin
  • noxiustoxin
  • Glycine