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Glycine 30 in iberiotoxin is a critical determinant of its specificity for maxi‐K versus K V channels
Author(s) -
Schroeder Nathan,
Mullmann Theodore J,
Schmalhofer W.A,
Gao Ying-Duo,
Garcia Maria L,
Giangiacomo Kathleen M
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03256-8
Subject(s) - iberiotoxin , charybdotoxin , mutagenesis , peptide , chemistry , biophysics , stereochemistry , biology , biochemistry , microbiology and biotechnology , mutation , potassium channel , membrane potential , gene
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 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 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.