Iberiotoxin (IbTX) is a remarkably selective α-K toxin peptide (α-KTx) inhibitor of the maxi-K channel. In contrast, the highly homologous charybdotoxin inhibits both the maxi-K and KV1.3 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 KV1.3 channels were monitored through dose-dependent displacement of specifically bound iodinated α-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. © 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
Schroeder, N., Mullmann, T. J., Schmalhofer, W. A., Gao, Y. D., Garcia, M. L., & Giangiacomo, K. M. (2002). Glycine 30 in iberiotoxin is a critical determinant of its specificity for maxi-K versus KV channels. FEBS Letters, 527(1–3), 298–302. https://doi.org/10.1016/S0014-5793(02)03256-8