A Novel Conus Peptide Ligand for K+Channels
作者： Michael Ferber , Annett Sporning , Gunnar Jeserich , Richard DeLaCruz , Maren Watkins
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摘要: Abstract Voltage-gated ion channels determine the membrane excitability of cells. Although many Conus peptides that interact with voltage-gated Na+ and Ca2+channels have been characterized, relatively few identified K+ channels. We describe a novelConus peptide interacts ShakerK+ channel, κM-conotoxin RIIIK from radiatus. The was chemically synthesized. is structurally similar to μ-conotoxins are sodium channel blockers, it does not affect any tested, but blocks Shaker Studies using mutants single residue substitutions reveal pore region channel. Introduction negative charge at 427 (K427D) greatly increases affinity toxin, whereas two other residues, Phe425 Thr449, drastically reduced toxin affinity. Based on results, teleost homolog theShaker TSha1 as target. Binding state-dependent, an IC50 20 nm for closed state 60 0 mV open
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