Two toxins from Conus striatus that individually induce tetanic paralysis.
We describe structural properties and biological activities of two related O-glycosylated peptide toxins isolated from injected (milked) venom of Conus striatus, a piscivorous snail that captures prey by injecting a venom that induces a violent, spastic paralysis. One 30 amino acid toxin is identified as kappaA-SIVA (termed s4a here), and another 37 amino acid toxin, s4b, corresponds to a putative peptide encoded by a previously reported cDNA. We confirm the amino acid sequences and carry out structural analyses of both mature toxins using multiple mass spectrometric techniques. These include electrospray ionization ion-trap mass spectrometry and nanoelectrospray techniques for small volume samples, as well as matrix-assisted laser desorption/ionization time of flight mass spectrometric analysis as a complementary method to assist in the determination of posttranslational modifications, including O-linked glycosylation. Physiological experiments indicate that both s4a and s4b induce intense repetitive firing of the frog neuromuscular junction, leading to a tetanic contracture in muscle fiber. These effects apparently involve modification of voltage-gated sodium channels in motor axons. Notably, application of either s4a or s4b alone mimics the biological effects of the whole injected venom on fish prey.
Kelley
Wayne P
WP
Department of Chemistry and The Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Schulz
Joseph R
JR
Jakubowski
Jennifer A
JA
Gilly
William F
WF
Sweedler
Jonathan V
JV
D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D020916:Conotoxins / Q000302:isolation & purification / Q000633:toxicity*; D052078:Conus Snail / Q000737:chemistry*; D018076:DNA, Complementary; D006031:Glycosylation; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D010243:Paralysis / Q000139:chemically induced*; D013746:Tetany / Q000139:chemically induced*
D020916:Conotoxins; D018076:DNA, Complementary