Purification, characterization, synthesis, and cloning of the lockjaw peptide from Conus purpurascens venom.
The major groups of Conus peptides previously characterized from fish-hunting cone snail venoms (the alpha-, mu-, and omega-conotoxins) all blocked neuromuscular transmission. A novel activity, the "lockjaw peptide", from the fish-hunting Conus purpurascens, caused a rigid (instead of flaccid) paralysis in fish and increased excitability at the neuromuscular junction (instead of a block). We report the purification, biological activity, biochemical and preliminary physiological characterization, and chemical synthesis of the lockjaw peptide and the sequence of a cDNA clone encoding its precursor. Taken together, the data lead us to conclude that the lockjaw peptide is a vertebrate-specific delta-conotoxin, which targets voltage-sensitive sodium channels. The sequence of the peptide, which we designate delta-conotoxin PVIA, is (O = 4-trans-hydroxyproline) EACYAOGTFCGIKOGLCCSEFCLPGVCFG-NH2. This is the first of a diverse spectrum of Conus peptides which are excitotoxins in vertebrate systems.
Shon
K J
KJ
Department of Biology, University of Utah, Salt Lake City 84112, USA.
Grilley
M M
MM
Marsh
M
M
Yoshikami
D
D
Hall
A R
AR
Kurz
B
B
Gray
W R
WR
Imperial
J S
JS
Hillyard
D R
DR
Olivera
B M
BM
D000200:Action Potentials / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D020916:Conotoxins; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry*; D009132:Muscles / Q000187:drug effects; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D011894:Rana pipiens; D017386:Sequence Homology, Amino Acid; D012908:Snails / Q000737:chemistry*
D020916:Conotoxins; D008978:Mollusk Venoms; D010455:Peptides; C093008:delta-conotoxin PVIA