An O-glycosylated neuroexcitatory conus peptide.
We purified and characterized a novel peptide from the venom of the fish-hunting cone snail Conus striatus that inhibits voltage-gated K+ channels. The peptide, kappaA-conotoxin SIVA, causes characteristic spastic paralytic symptoms when injected into fish, and in frog nerve-muscle preparations exposed to the toxin, repetitive action potentials are seen in response to a single stimulus applied to the motor nerve. Other electrophysiological tests on diverse preparations provide evidence that is consistent with the peptide blocking K+ channels. The peptide has three disulfide bonds; the locations of Cys residues indicate that the spastic peptide may be the first and defining member of a new family of Conus peptides, the kappaA-conotoxins, which are structurally related to, but pharmacologically distinct from, the alphaA-conotoxins. This 30 AA tricyclic toxin has several characteristics not previously observed in Conus peptides. In addition to the distinctive biological and physiological activity, a novel biochemical feature is the unusually long linear N-terminal tail (11 residues) which contains one O-glycosylated serine at position 7. This is the first evidence for O-glycosylation as a posttranslational modification in a biologically active Conus peptide.
Craig
A G
AG
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, San Diego, California 92186-5800, USA.
Zafaralla
G
G
Cruz
L J
LJ
Santos
A D
AD
Hillyard
D R
DR
Dykert
J
J
Rivier
J E
JE
Gray
W R
WR
Imperial
J
J
DelaCruz
R G
RG
Sporning
A
A
Terlau
H
H
West
P J
PJ
Yoshikami
D
D
Olivera
B M
BM
D000200:Action Potentials / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D020916:Conotoxins; D005399:Fishes; D005728:Ganglia, Sympathetic / Q000187:drug effects; D006031:Glycosylation; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D011898:Ranidae; D012908:Snails; D013035:Spasm / Q000139:chemically induced / Q000503:physiopathology
D020916:Conotoxins; D008978:Mollusk Venoms; D010455:Peptides; C115957:kappaA-conotoxin SIVA