An O-glycosylated neuroexcitatory conus peptide.
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| Abstract |
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.
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| Authors | A G Craig, G Zafaralla, L J Cruz, A D Santos, D R Hillyard, J Dykert, J E Rivier, W R Gray, J Imperial, R G DelaCruz, A Sporning, H Terlau, P J West, D Yoshikami, B M Olivera |
| Journal | Biochemistry (Biochemistry) Vol. 37 Issue 46 Pg. 16019-25 (Nov 17 1998) ISSN: 0006-2960 [Print] United States |
| PMID | 9819194 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.) |
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