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

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.