Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Asparagine
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Cells, Cultured
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Glycine / chemistry*
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Humans
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Kv1.3 Potassium Channel
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Large-Conductance Calcium-Activated Potassium Channels
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Molecular Sequence Data
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Mutation
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Peptides / chemistry
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Peptides / genetics
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Peptides / metabolism*
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Potassium Channels / metabolism*
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Potassium Channels, Calcium-Activated / metabolism*
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Potassium Channels, Voltage-Gated*
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Protein Conformation
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Scorpion Venoms / genetics
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Scorpion Venoms / metabolism
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Sequence Homology, Amino Acid
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Substrate Specificity
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Toxins, Biological / metabolism*
Substances
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KCNA3 protein, human
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Kv1.3 Potassium Channel
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Large-Conductance Calcium-Activated Potassium Channels
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Peptides
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Potassium Channels
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Potassium Channels, Calcium-Activated
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Potassium Channels, Voltage-Gated
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Scorpion Venoms
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Toxins, Biological
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Asparagine
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iberiotoxin
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noxiustoxin
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Glycine