AN O-GLYCOSYLATED NEUROEXCITATORY CONUS PEPTIDE

We purified and characterized a novel peptide from the venom of the fi sh-hunting cone snail Conus striatus that inhibits voltage-gated K+ ch annels. The peptide, kappa A-conotoxin SIVA, causes characteristic spa stic paralytic symptoms when injected into fish, and in frog nerve-mus cle preparations exposed to the toxin, repetitive action potentials ar e seen in response to a single stimulus applied to the motor nerve. Ot her electrophysiological tests on diverse preparations provide evidenc e that is consistent with the peptide blocking K+ channels. The peptid e has three disulfide bonds; the locations of Cys residues indicate th at the spastic peptide may be the first and defining member of a new f amily of Conus peptides, the kappa A-conotoxins, which are structurall y related to, but pharmacologically distinct from, the alpha A-conotox ins. This 30 AA tricyclic toxin has several characteristics not previo usly observed in Conus peptides. In addition to the distinctive biolog ical and physiological activity, a novel biochemical feature is the un usually long linear N-terminal tail (11 residues) which contains one O -glycosylated serine at position 7. This is the first evidence for O-g lycosylation as a posttranslational modification in a biologically act ive Conus peptide.