Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 24 July 1998:
Vol. 281. no. 5376, pp. 575 - 578
DOI: 10.1126/science.281.5376.575

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, sigma -conotoxin GVIIIA, was purified on the basis of its ability to inactivate the 5-HT3 receptor, an excitatory serotonin-gated ion channel. sigma -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. sigma -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
   Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Conus Venoms: A Rich Source of Novel Ion Channel-Targeted Peptides.
H. TERLAU and B. M. OLIVERA (2004)
Physiol Rev 84, 41-68
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)