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Science 24 July 1998: Vol. 281. no. 5376, pp. 575 - 578 DOI: 10.1126/science.281.5376.575
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Reports
Inactivation of a Serotonin-Gated Ion Channel by a Polypeptide Toxin from Marine Snails
Laura J. England,
Julita Imperial,
Richard Jacobsen,
A. Grey Craig,
Joseph Gulyas,
Mateen Akhtar,
Jean Rivier,
David Julius,
*
Baldomero M. Olivera
The venom of predatory marine snails is a rich source of natural
products that act on specific receptors and ion channels within the
mammalian nervous system. A 41-amino acid peptide, -conotoxin
GVIIIA, was purified on the basis of its ability to inactivate the
5-HT3 receptor, an excitatory serotonin-gated ion channel.
-Conotoxin contains a brominated tryptophan residue, which may be
important for peptide activity because the endogenous ligand for the
5-HT3 receptor is a hydroxylated derivative of tryptophan.
-Conotoxin inactivates the 5-HT3 receptor through competitive antagonism and is a highly selective inhibitor of this
receptor. Serotonin receptors can now be included among the molecular
targets of natural polypeptide neurotoxins.
L. J. England and D. Julius, Department of Cellular and
Molecular Pharmacology, University of California, San Francisco, CA
94143-0450, USA. J. Imperial, R. Jacobsen, B. M. Olivera,
Department of Biology, University of Utah, Salt Lake City, UT
84112-0840, USA. A. G. Craig, J. Gulyas, M. Akhtar, J. Rivier,
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute
for Biological Studies, La Jolla, CA 92037, USA.
*
To whom correspondence should be addressed. E-mail:
julius{at}socrates.ucsf.edu
Read the Full Text
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
- Conus Peptides: Biodiversity-based Discovery and Exogenomics.
- B. M. Olivera (2006)
J. Biol. Chem.
281, 31173-31177
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- Identification of a Novel Class of Nicotinic Receptor Antagonists: DIMERIC CONOTOXINS VxXIIA, VxXIIB, and VxXIIC FROM CONUS VEXILLUM.
- M. Loughnan, A. Nicke, A. Jones, C. I. Schroeder, S. T. Nevin, D. J. Adams, P. F. Alewood, and R. J. Lewis (2006)
J. Biol. Chem.
281, 24745-24755
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- The Tarantula Toxin Psalmotoxin 1 Inhibits Acid-sensing Ion Channel (ASIC) 1a by Increasing Its Apparent H+ Affinity.
- X. Chen, H. Kalbacher, and S. Grunder (2005)
J. Gen. Physiol.
126, 71-79
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- Conus Venoms: A Rich Source of Novel Ion Channel-Targeted Peptides.
- H. TERLAU and B. M. OLIVERA (2004)
Physiol Rev
84, 41-68
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- Characterization of a Novel Gastropod Toxin (6-Bromo-2-mercaptotryptamine) That Inhibits Shaker K Channel Activity.
- W. P. Kelley, A. M. Wolters, J. T. Sack, R. A. Jockusch, J. C. Jurchen, E. R. Williams, J. V. Sweedler, and W. F. Gilly (2003)
J. Biol. Chem.
278, 34934-34942
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- Identification of a Neuropeptide Modified with Bromine as an Endogenous Ligand for GPR7.
- R. Fujii, H. Yoshida, S. Fukusumi, Y. Habata, M. Hosoya, Y. Kawamata, T. Yano, S. Hinuma, C. Kitada, T. Asami, et al. (2002)
J. Biol. Chem.
277, 34010-34016
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- A conotoxin from Conus textile with unusual posttranslational modifications reduces presynaptic Ca2+ influx.
- A. C. Rigby, E. Lucas-Meunier, D. E. Kalume, E. Czerwiec, B. Hambe, I. Dahlqvist, P. Fossier, G. Baux, P. Roepstorff, J. D. Baleja, et al. (1999)
PNAS
96, 5758-5763
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- Single Amino Acid Substitutions in kappa -Conotoxin PVIIA Disrupt Interaction with the Shaker K+ Channel.
- R. B. Jacobsen, E. D. Koch, B. Lange-Malecki, M. Stocker, J. Verhey, R. M. Van Wagoner, A. Vyazovkina, B. M. Olivera, and H. Terlau (2000)
J. Biol. Chem.
275, 24639-24644
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