A NONCOMPETITIVE PEPTIDE INHIBITOR OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR FROM CONUS-PURPURASCENS VENOM

A paralytic peptide, psi-conotoxin PIIIE has been purified and charact erized from Conus purpurascens venom. Electrophysiological studies ind icate that the peptide inhibits the nicotinic acetylcholine receptor ( nAChR). However, the peptide does not block the binding of alpha-bunga rotoxin, a competitive nAChR antagonist. Thus, psi-conotoxin PIIIE app ears to inhibit the receptor al a site other than the acetylcholine-bi nding site. As ascertained by sequence analysis, mass spectrometry, an d chemical synthesis, the peptide has the following covalent structure : HOOCCLYGKCRRYOGCSSASCCQR (O = 4-trans hydroxyproline; * indicates a n amidated C-terminus). The disulfide connectivity of the toxin is unr elated to the alpha- or the alpha A-conotoxins, the Conus peptide fami lies that are competitive inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+ channel blockers).