α-Conotoxin EI, a New Nicotinic Acetylcholine Receptor Antagonist with Novel Selectivity

Jennifer S. Martinez, Baldomero M. Olivera, William R. Gray, A. Grey Craig, Duncan R. Groebe, Stewart N. Abramson, J. Michael Mclntosh

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

We report the isolation and characterization of a novel nicotinic acetylcholine receptor (nAChR) ligand. The toxin is an 18 amino acid peptide and is the first reported α-conotoxin from an Atlantic fish-hunting Conus. The peptide was purified from the venom of Conus ermineus and is called a-conotoxin Ei. The sequence diverges from that of previously isolated α-conotoxins. We demonstrate that this structural divergence has functional consequences. In Torpedo nAChRs, α-conotoxin Ei selectively binds the agonist site near the aId subunit interface in contrast to α-conotoxin Mi which selectively targets the α/γ agonist binding site. In mammalian nAChRs α-conotoxin Ei shows high affinity for both the α/δ and α/γ subunit interfaces (with some preference for the α/δ site), whereas α-conotoxin Mi is highly selective for the α/δ ligand binding site. The sequence of the peptide is: Arg-Asp-Hyp-Cys-Cys-Tyr- His-Pro-Thr-Cys-Asn-Met-Ser-Asn-Pro-Gln-Ile-Cys-NH2, with disulfide bridging between Cys4-Cys10 and Cys5-Cys18, analogous to those of previously described α-conotoxins. This sequence has been verified by total chemical synthesis. Thus, α-conotoxin Ei is a newly-available tool with unique structure and function for characterization of nAChRs.

Original languageEnglish (US)
Pages (from-to)14519-14526
Number of pages8
JournalBiochemistry
Volume34
Issue number44
DOIs
StatePublished - Nov 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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