Inactivation of a Serotonin-Gated Ion Channel by a Polypeptide Toxin from Marine Snails

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Science  24 Jul 1998:
Vol. 281, Issue 5376, pp. 575-578
DOI: 10.1126/science.281.5376.575

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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, σ-conotoxin GVIIIA, was purified on the basis of its ability to inactivate the 5-HT3 receptor, an excitatory serotonin-gated ion channel. σ-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. σ-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.

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