Abstract
Charybdotoxin, a peptide neurotoxin of known molecular structure, blocks Shaker K+ channels by binding to a receptor at the outer opening of the ion conduction pathway. Analysis of variants of CTX at position 29 and of Shaker at position 449 shows that these two residues interact closely in the channel-toxin complex. The CTX mutation M29I leads to a slight strengthening of block when tested on Shaker-449T; the same CTX mutation weakens block 1700-fold when tested on Shaker-449F. The known position of CTX-29 on the toxin's interaction surface thus locates Shaker-449 within 5 A of the pore axis of the closed channel. All four subunits must carry the 449F mutation to produce a highly toxin-insensitive channel.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Charybdotoxin / chemistry*
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Charybdotoxin / genetics
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Charybdotoxin / metabolism
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Charybdotoxin / pharmacology
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Drosophila Proteins
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Drosophila melanogaster / genetics
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Ion Channel Gating / drug effects
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Lysine / chemistry
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Molecular Sequence Data
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Oocytes
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Phenylalanine / chemistry
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Potassium / metabolism
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Potassium Channels / chemistry*
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Potassium Channels / drug effects
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Potassium Channels / genetics
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Potassium Channels / metabolism
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Protein Binding
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Protein Conformation*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Scorpions / genetics
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Shaker Superfamily of Potassium Channels
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Threonine / chemistry
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Transfection
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Xenopus laevis
Substances
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Drosophila Proteins
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Potassium Channels
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Recombinant Fusion Proteins
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Sh protein, Drosophila
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Shaker Superfamily of Potassium Channels
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charybdotoxin receptor
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Charybdotoxin
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Threonine
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Phenylalanine
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Lysine
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Potassium