A noncompetitive peptide inhibitor of the nicotinic acetylcholine receptor from Conus purpurascens venom.
A paralytic peptide, psi-conotoxin Piiie has been purified and characterized from Conus purpurascens venom. Electrophysiological studies indicate that the peptide inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does not block the binding of alpha-bungarotoxin, a competitive nAChR antagonist. Thus, psi-conotoxin Piiie appears to inhibit the receptor at a site other than the acetylcholine-binding site. As ascertained by sequence analysis, mass spectrometry, and chemical synthesis, the peptide has the following covalent structure: HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the alpha- or the alphaA-conotoxins, the Conus peptide families that are competitive inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+ channel blockers).
Shon
K J
KJ
Department of Biology and Pathology, University of Utah, Salt Lake City, Utah, 84112, USA.
Grilley
M
M
Jacobsen
R
R
Cartier
G E
GE
Hopkins
C
C
Gray
W R
WR
Watkins
M
M
Hillyard
D R
DR
Rivier
J
J
Torres
J
J
Yoshikami
D
D
Olivera
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006054:Goldfish; D051379:Mice; D008969:Molecular Sequence Data; D009469:Neuromuscular Junction / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D012908:Snails / Q000737:chemistry*; D014101:Torpedo; D020960:omega-Conotoxins
D018733:Nicotinic Antagonists; D010455:Peptides; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D020960:omega-Conotoxins; C107492:psi-conotoxin PIIIE