A new family of Conus peptides targeted to the nicotinic acetylcholine receptor.
In this work, a new family of Conus peptides, the alpha A-conotoxins, which target the nicotinic acetylcholine receptor, is defined. The first members of this family have been characterized from the eastern Pacific species, Conus purpurascens (the purple cone); three peptides that cause paralysis in fish were purified and characterized from milked venom. The sequence and disulfide bonding pattern of one of these, alpha A-conotoxin PIVA, is as follows: [formula: see text] where O represents trans-4-hydroxyproline. The two other peptides purified from C. purpurascens venom are the under-hydroxylated derivatives, [Pro13]alpha A-conotoxin PIVA and [Pro7,13]alpha A-conotoxin PIVA. The peptides have been chemically synthesized in a biologically active form. Both electrophysiological experiments and competition binding with alpha-bungarotoxin demonstrate that alpha A-PIVA acts as an antagonist of the nicotinic acetylcholine receptor at the postsynaptic membrane.
Hopkins
C
C
Department of Biology, University of Utah, Salt Lake City 84112, USA.
Grilley
M
M
Miller
C
C
Shon
K J
KJ
Cruz
L J
LJ
Gray
W R
WR
Dykert
J
J
Rivier
J
J
Yoshikami
D
D
Olivera
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000302:isolation & purification* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012908:Snails / Q000737:chemistry*; D013329:Structure-Activity Relationship
D020916:Conotoxins; D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D011978:Receptors, Nicotinic; C104576:alphaA-conotoxin PIVA