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          Institute: MPI für experimentelle Medizin     Collection: MCN     Display Documents



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ID: 42781.0, MPI für experimentelle Medizin / MCN
A novel Conus peptide ligand for K+ channels
Authors:Ferber, Michael; Sporning, Annett; Jeserich, Gunnar; DeLaCruz, Richard; Watkins, Maren; Olivera, Baldomero M.; Terlau, Heinrich
Language:English
Date of Publication (YYYY-MM-DD):2003-01-24
Title of Journal:Journal of Biological Chemistry
Journal Abbrev.:J. Biol. Chem.
Volume:278
Issue / Number:4
Start Page:2177
End Page:2183
Review Status:Peer-review
Audience:Experts Only
Abstract / Description: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 have been identified that interact with K+ channels. We describe a novel Conus peptide that interacts with the Shaker K+ channel, M-kappa-conotoxin RIIIK from Conus radiatus. The peptide was chemically synthesized. Although M- kappa-conotoxin RIIIK is structurally similar to the mu- conotoxins that are sodium channel blockers, it does not affect any of the sodium channels tested, but blocks Shaker K+ channels. Studies using Shaker K+ channel mutants with single residue substitutions reveal that the peptide interacts with the pore region of the channel. Introduction of a negative charge at residue 427 (K427D) greatly increases the affinity of the toxin, whereas the substitutions at two other residues, Phe(425) and Thr (449), drastically reduced toxin affinity. Based on the Shaker results, a teleost homolog of the Shaker K+ channel, TSha1 was identified as a M-kappa-conotoxin RIIIK target. Binding of M-kappa-conotoxin RIIIK is state-dependent, with an IC50 of 20 nM for the closed state and 60 nm at 0 mV for the open state of TSha1 channels.
Comment of the Author/Creator:Date: 2003, JAN 24
External Publication Status:published
Document Type:Article
Communicated by:Heinrich Terlau
Affiliations:MPI für experimentelle Medizin/MCN
External Affiliations:Univ Utah, Dept Biol, 257 South 1400 East, Salt Lake City, UT; 84112 USA; Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA; Univ Osnabruck, Dept Anim Physiol, D-40069 Osnabruck, Germany;
Identifiers:ISI:000180562000015 [ID No:1]
ISSN:0021-9258 [ID No:2]
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