alpha-Conotoxin EI, a new nicotinic acetylcholine receptor antagonist with novel selectivity

Biochemistry. 1995 Nov 7;34(44):14519-26. doi: 10.1021/bi00044a030.


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 alpha-conotoxin from an Atlantic fish-hunting Conus. The peptide was purified from the venom of Conus ermineus and is called alpha-conotoxin EI. The sequence diverges from that of previously isolated alpha-conotoxins. We demonstrate that this structural divergence has functional consequences. In Torpedo nAChRs, alpha-conotoxin EI selectively binds the agonist site near the alpha/delta subunit interface in contrast to alpha-conotoxin MI which selectively targets the alpha/gamma agonist binding site. In mammalian nAChRs alpha-conotoxin EI shows high affinity for both the alpha/delta and alpha/gamma subunit interfaces (with some preference for the alpha/delta site), whereas alpha-conotoxin MI is highly selective for the alpha/delta 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 alpha-conotoxins. This sequence has been verified by total chemical synthesis. Thus, alpha-conotoxin EI is a newly-available tool with unique structure and function for characterization of nAChRs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conotoxins*
  • Fishes
  • Molecular Sequence Data
  • Nicotinic Antagonists / isolation & purification*
  • Nicotinic Antagonists / metabolism
  • Peptides / isolation & purification*
  • Peptides / metabolism
  • Radioligand Assay
  • Receptors, Nicotinic / metabolism
  • Toxins, Biological / isolation & purification*
  • Toxins, Biological / metabolism


  • Conotoxins
  • Nicotinic Antagonists
  • Peptides
  • Receptors, Nicotinic
  • Toxins, Biological
  • conotoxin EI