2004
DOI: 10.1074/jbc.m309654200
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The A-superfamily of Conotoxins

Abstract: The generation of functional novelty in proteins encoded by a gene superfamily is seldom well documented. In this report, we define the A-conotoxin superfamily, which is widely expressed in venoms of the predatory cone snails (Conus), and show how gene products that diverge considerably in structure and function have arisen within the same superfamily. A cDNA clone encoding ␣-conotoxin GI, the first conotoxin characterized, provided initial data that identified the A-superfamily. Conotoxin precursors in the A-… Show more

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Cited by 122 publications
(46 citation statements)
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“…An unusual feature of the conotoxins is that while the mature toxin peptides are highly variable in sequence, the precursor proteins are highly conserved. The signal sequence region is practically invariant among the different ␣-conotoxin precursors, and this remains true even for phylogenetically distant Conus species (13,14). Also, the 3Ј-untranslated region of the ␣-conotoxin mRNA is highly conserved.…”
Section: Cloning Of ␣-Conotoxinmentioning
confidence: 88%
See 1 more Smart Citation
“…An unusual feature of the conotoxins is that while the mature toxin peptides are highly variable in sequence, the precursor proteins are highly conserved. The signal sequence region is practically invariant among the different ␣-conotoxin precursors, and this remains true even for phylogenetically distant Conus species (13,14). Also, the 3Ј-untranslated region of the ␣-conotoxin mRNA is highly conserved.…”
Section: Cloning Of ␣-Conotoxinmentioning
confidence: 88%
“…The toxin-encoding gene is homologous to peptides that are members of the A-superfamily of Conus toxins. This superfamily consists of peptides that act on nAChRs, potassium channels and sodium channels (14,16,17).…”
Section: ␣-Buia Distinguishes Among Neuronal Nachrsmentioning
confidence: 99%
“…The peptide is 16 residues in length, with two disulfide bonds. ␣-CTx PeIA Discriminates between ␣9␣10 and ␣7 nAChRs␣-CTx PeIA belongs to the A superfamily, as do the majority of Conus peptides that are known to affect the function of nAChRs (37). The spacing between Cys residues, four amino acids in the first loop and seven in the second loop, is typical of several previously isolated ␣-CTxs of the ␣4/7 family such as MII and GIC, which preferentially target non-muscle nAChRs (18,35).…”
Section: Discussionmentioning
confidence: 99%
“…The only multimeric protein described so far from Conus venoms is a phospholipase (17). In contrast, there are numerous examples of heterodimers among venom toxins from several other genera including ants, spiders, scorpions, and snakes (17)(18)(19)(20)(21)(22)(23). Additionally, -neurotoxins from snake venom can form homodimers in solution at physiological concentrations, raising implications for both the mechanism of polypeptide chain folding during biosynthesis of the toxins and for their interaction with nAChRs (4).…”
mentioning
confidence: 99%