A molluskivorous Conus toxin: conserved frameworks in conotoxins (original) (raw)
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Mollusc-specific toxins from the venom of Conus textile neovicarius
European journal of biochemistry / FEBS, 1991
Three peptide toxins exhibiting strong paralytic activity to molluscs, but with no paralytic effects on arthropods or vertebrates, were purified from the venom of the molluscivorous snail Conus textile neovicarius from the Red Sea. The amino acid sequences of these mollusc specific toxins are: TxIA, WCKQSGEMCNLLDQNCCDGYCI-VLVCT (identical to the so called 'King Kong peptide'); TxIB, WCKQSGEMCNVLDQNCCDGYCIVFVCT; TxIIA, WGGYSTYC gamma VDS gamma CCSDNCVRSYCT (gamma = gamma-carboxyglutamate). There is a similarity of the Cys framework of these toxins to that of the omega-conotoxins; however, their net negative charges, high content of hydrophobic residues and uneven number of Cys residues in TxIIA, are highly unusual for conotoxins. When assayed on isolated cultured Aplysia neurons, all three toxins induced membrane depolarization and spontaneous repetitive firing. The TxI toxins also induce a marked prolongation of the action potential duration, which is sodium dependent. These...
Isolation and structure of a peptide toxin from the marine snail Conus magus
Archives of Biochemistry and Biophysics, 1982
A ll-residue peptide toxin has been isolated from the venom of the marine snail Conus magus. Its amino acid sequence, Gly-Arg-Cys-Cys-His-Pro-Ala-Cys-Gly-Lys-Asn-Tyr-Ser-Cys-NHz, is homologous with those of the previously described conotoxins GI, GII, and GIA from Conus geographus. The new peptide, conotoxin MI, is two to three times more active than the others, and is presumed to act as they do at the acetylcholine receptor of vertebrate neuromuscular junctions. 329
Peptides, 2013
Cone snail venoms provide a largely untapped source of novel peptide drug leads. To enhance the discovery phase, a detailed comparative proteomic analysis was undertaken on milked venom from the mollusk-hunting cone snail, Conus textile, from three different geographic locations (Hawai'i, American Samoa and Australia's Great Barrier Reef). A novel milked venom conopeptide rich in post-translational modifications was discovered, characterized and named ␣-conotoxin TxIC. We assign this conopeptide to the 4/7 ␣-conotoxin family based on the peptide's sequence homology and cDNA pre-propeptide alignment. Pharmacologically, ␣-conotoxin TxIC demonstrates minimal activity on human acetylcholine receptor models (100 M, <5% inhibition), compared to its high paralytic potency in invertebrates, PD 50 = 34.2 nMol kg −1 . The non-post-translationally modified form, [Pro] 2,8 [Glu] 16 ␣-conotoxin TxIC, demonstrates differential selectivity for the ␣32 isoform of the nicotinic acetylcholine receptor with maximal inhibition of 96% and an observed IC 50 of 5.4 ± 0.5 M. Interestingly its comparative PD 50 (3.6 Mol kg −1 ) in invertebrates was ∼100 fold more than that of the native peptide. Differentiating ␣-conotoxin TxIC from other ␣-conotoxins is the high degree of post-translational modification (44% of residues). This includes the incorporation of ␥-carboxyglutamic acid, two moieties of 4-trans hydroxyproline, two disulfide bond linkages, and C-terminal amidation. These findings expand upon the known chemical diversity of ␣-conotoxins and illustrate a potential driver of toxin phyla-selectivity within Conus.
Peptide toxins from Conus geographus venom
Journal of Biological Chemistry, 1981
Three homologous toxic peptides which cause postsynaptic inhibition at the vertebrate neuromuscar junction have been purified from the venom of the marine snail Conus geographus.
Discovery of a new subclass of α-conotoxins in the venom of Conus australis
Toxicon : official journal of the International Society on Toxinology, 2014
Cone snails (Conus sp.) are poisonous animals that can be found in all oceans where they developed a venomous strategy to prey or to defend. The venom of these species contains an undeniable source of unique and potent pharmacologically active compounds. Their peptide compounds, called conotoxins, are not only interesting for the development of new pharmaceutical ligands, but they are also useful for studying their broad spectrum of targets. One conotoxin family in particular, the α-conotoxins, acts on nicotinic acetylcholine receptors (nAChRs) which dysfunctions play important roles in pathologies such as epilepsy, myasthenic syndromes, schizophrenia, Parkinson's disease and Alzheimer's disease. Here we define a new subclass of the α-conotoxin family. We purified the venom of a yet unexplored cone snail species, i.e. Conus australis, and we isolated a 16-amino acid peptide named α-conotoxin AusIA. The peptide has the typical α-conotoxin CC-Xm-C-Xn-C framework, but both loop...
Purification and sequence of a presynaptic peptide toxin from Conus geographus venom
Biochemistry, 1984
A novel toxin, o-conotoxh (w-CgTX), from the venom of the fish-eating marine mollusc Conus geogruphus has been purified and biochemically characterized. Recently, this o-conotoxin has been shown to inhibit the voltageactivated entry of Ca2+, thus providing a potentially powerful probe for exploring the vertebrate presynaptic terminal [Kerr, L. M., ikami, R. D. Zeikus, and W. R. Gray, unpublished results;
Journal of marine science, 2021
Conus loroisii is a marine vermivorous snail found profusely in the southern seas of India. They harbor several toxic peptide components commonly called as 'conotoxins'. In this study, we have identified and sequenced five conotoxins using proteome based tandem mass spectrometry analysis through Data analysis 4.1 software. Among them, we found Lo959 as contryphan which is previously described. All other conotoxins Lo1702, Lo1410, Lo1385 and Lo1686 belong to M-Superfamily conotoxins and novel to C. loroisii. Lo1410 is completely novel to conotoxin research with 3 disulfides and the amino acid sequence is derived as CCSTNCAVCIPCCP. All the identified M-Superfamily conotoxins are sub categorised to mini M2 superfamily conotoxins. Lo1702 and Lo1686 possess C-terminal amidation which is the key feature in conotoxins. Moreover, we have screened the natural venom for the occurrence of toxicity in the zebrafish model and brine shrimp.
Biochemistry, 2005
Most of the >50 000 different pharmacologically active peptides in Conus venoms belong to a small number of gene superfamilies. In this work, the M-conotoxin superfamily is defined using both biochemical and molecular criteria. Novel excitatory peptides purified from the venoms of the molluscivorous species Conus textile and Conus marmoreus all have a characteristic pattern of Cys residues previously found in the µ-, κM-, and ψ-conotoxins (CC-C-C-CC). The new peptides are smaller (12-19 amino acids) than the µ-, κM-, and ψ-conotoxins (22-24 amino acids). One peptide, mr3a, was chemically synthesized in a biologically active form. Analysis of the disulfide bridges of a natural peptide tx3c from C. textile and synthetic peptide mr3a from C. marmoreus showed a novel pattern of disulfide connectivity, different from that previously established for the µ-and ψ-conotoxins. Thus, these peptides belong to a new group of structurally and pharmacologically distinct conotoxins that are particularly prominent in the venoms of mollusc-hunting Conus species. Analysis of cDNA clones encoding the novel peptides as well as those encoding µ-, κM-, and ψ-conotoxins revealed highly conserved amino acid residues in the precursor sequences; this conservation in both amino acid sequence and in the Cys pattern defines a gene superfamily, designated the M-conotoxin superfamily. The peptides characterized can be provisionally assigned to four distinct groups within the M-superfamily based on sequence similarity within and divergence between each group. A notable feature of the superfamily is that two distinct structural frameworks have been generated by changing the disulfide connectivity on an otherwise conserved Cys pattern.
Saudi Journal of Biological Sciences
Venom of Conus inscriptus, a vermivorous cone snail found abundantly in the southern coastal waters was studied to yield conotoxins through proteomic analysis. A total of 37 conotoxins (4 with single disulfide bonds, 20 with two disulfide bonds and 11 three disulfide-bonded peptides) were identified using mass spectrometric analysis. Among them, amino acid sequences of 11 novel conopeptides with one, two and three disulfides belonging to different classes were derived through manual de novo sequencing. Based on the established primary sequence, they were pharmacologically classified into a conotoxins, m conotoxins and contryphans. Except In1696 all other conopeptides have undergone C-terminal amidation. The natural venom exhibited 50% lethality at 304.82 mg/mL against zebrafish embryo and 130.31 mg/mL against brine shrimp nauplii. The anticonvulsant study of natural venom effectively reduced the locomotor activity against pentylenetetrazole (PTZ) treated zebrafish. This concludes that the venom peptides from Conus inscriptus exhibit potential anticonvulsant function, which leads to the discovery of lead molecules against seizures.