Mollusc‐specific toxins from the venom of <i>Conus textile neovicarius</i>

Fainzilber, Mike; Gordon, Dalia; Hasson, Arik; Spira, Micha Ε.; Zlotkin, Eliahu

doi:10.1111/j.1432-1033.1991.tb16412.x

Cited by 96 publications

(90 citation statements)

References 29 publications

(27 reference statements)

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“…Both peptides showed negligible effects on neuromuscular transmission at concentrations up to 124 and 126 nM, respectively. 3 …”

Section: Purification Of Conotoxins-conotoxins Isolated Frommentioning

confidence: 99%

“…Conotoxins can be classified into several families based on the number and pattern of disulfide bonds and biological activities (1,2). Members of a single family of conotoxins share similar protein folding but in some cases exhibit different biological activities (3)(4)(5). These differences in biological activities are due to their ability to bind with specific ion channels or receptors (6).…”

mentioning

confidence: 99%

“…The conotoxins with two disulfide bonds can have three possible monomeric conformations: "globular" having a Greek ""-like conformation formed by interlocking disulfide bridges between C 1 -C 3 and C 2 -C 4 , 1 "string of independent bead" conformation with C 1 -C 2 and C 3 -C 4 , or a "ribbon topology" with C 1 -C 4 and C 2 -C 3 bond formation (11). Native ␣-and -conotoxins, however, possess an identical disulfide bonding pattern (C 1 -C 3 , C 2 -C 4 ) and globular conformation (12,13).…”

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confidence: 99%

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λ-Conotoxins, a New Family of Conotoxins with Unique Disulfide Pattern and Protein Folding

Balaji¹,

Ohtake²,

Sato³

et al. 2000

Journal of Biological Chemistry

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Conotoxins are multiple disulfide-bonded peptides isolated from marine cone snail venom. These toxins have been classified into several families based on their disulfide pattern and biological properties. Here, we report a new family of Conus peptides, which have a novel cysteine motif. Three peptides of this family (CMrVIA, CMrVIB, and CMrX) have been purified from Conus marmoreus venom, and their structures have been determined. Their amino acid sequences are VCCGYK-LCHOC (CMrVIA), NGVCCGYKLCHOC (CMrVIB), and GICCGVSFCYOC (CMrX), where O represents 4-transhydroxyproline. Two of these peptides (CMrVIA and CMrX) have been chemically synthesized. Using a selective protection and deprotection strategy during disulfide bond formation, peptides with both feasible cysteine-pairing combinations were generated. The disulfide pattern (C 1 -C 4 , C 2 -C 3 ) in native toxins was identified by their co-elution with the synthetic disulfideisomeric peptides on reverse-phase high pressure liquid chromatography. Although cysteine residues were found in comparable positions with those of ␣-conotoxins, these toxins exhibited a distinctly different disulfide bonding pattern; we have named this new family " -conotoxins." CMrVIA and CMrX induced different biological effects when injected intra-cerebroventricularly in mice; CMrVIA induces seizures, whereas CMrX induces flaccid paralysis. The synthetic peptide with -conotoxin folding is about 1150-fold more potent in inducing seizures than the mispaired isomer with ␣-conotoxin folding. Thus it appears that the unique disulfide pattern, and hence the "ribbon" conformation, in -conotoxins is important for their biological activity.Conotoxins are biologically active peptide toxins isolated from venomous marine cone snails. They are typically small disulfide-rich peptides containing 11-30 amino acid residues. Conotoxins can be classified into several families based on the number and pattern of disulfide bonds and biological activities (1, 2). Members of a single family of conotoxins share similar protein folding but in some cases exhibit different biological activities (3-5). These differences in biological activities are due to their ability to bind with specific ion channels or receptors (6). Some of these conotoxins are used as tools in investigating receptor structure and function (2) and ion channel geometry (7). The structurally constrained scaffolds of conotoxins are utilized as a template for protein engineering to create chimeric proteins (8, 9).Conotoxins, like toxins from other venoms, evolve rapidly by positive Darwinian selection (10). The specificity of conotoxins is due to their disulfide bonding framework and specific amino acids in inter-cysteine loops. The high density of disulfides in conotoxins plays a vital role in their stability and imposes a distinct protein folding with a specific orientation of hypervariable loop regions. The diversity in conotoxins is also achieved through disulfide pairings (see "Discussion").The conotoxins with two disulfide bonds can have th...

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“…Both peptides showed negligible effects on neuromuscular transmission at concentrations up to 124 and 126 nM, respectively. 3 …”

Section: Purification Of Conotoxins-conotoxins Isolated Frommentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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λ-Conotoxins, a New Family of Conotoxins with Unique Disulfide Pattern and Protein Folding

Balaji¹,

Ohtake²,

Sato³

et al. 2000

Journal of Biological Chemistry

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“…Lyophilized venom extract (1000 mg, from five cone snails) was dissolved in 0.2 M ammonium acetate buffer (pH 7.5) (17,20) and chromatographed on a Sephadex G-50 superfine column (2.5 ϫ 92 cm) equilibrated with 0.2 M ammonium acetate buffer (pH 7.5) and eluted with a flow rate of 10.3 ml/h (Fig. 1A).…”

Section: Methodsmentioning

confidence: 99%

The First γ-Carboxyglutamic Acid-containing Contryphan

Hansson

Eliasson

et al. 2004

Journal of Biological Chemistry

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Contryphans constitute a group of conopeptides that are known to contain an unusual density of post-translational modifications including tryptophan bromination, amidation of the C-terminal residue, leucine, and tryptophan isomerization, and proline hydroxylation. Here we report the identification and characterization of a new member of this family, glacontryphan-M from the venom of Conus marmoreus. This is the first known example of a contryphan peptide carrying glutamyl residues that have been post-translationally carboxylated to ␥-carboxyglutamyl (Gla) residues. The amino acid sequence of glacontryphan-M was determined using automated Edman degradation and electrospray ionization mass spectrometry. The amino acid sequence of the peptide is: Asn-Gla-Ser-Gla-Cys-Pro-D-Trp-His-Pro-Trp-Cys. As with most other contryphans, glacontryphan-M is amidated at the C terminus and maintains the five-residue intercysteine loop. The occurrence of a D-tryptophan residue was confirmed by chemical synthesis and HPLC elution profiles. Using fluorescence spectroscopy we demonstrated that the Gla-containing peptide binds calcium with a K D of 0.63 mM. Cloning of the full-length cDNA encoding glacontryphan-M revealed that the primary translation product carries an N-terminal signal/ propeptide sequence that is homologous to earlier reported contryphan signal/propeptide sequences up to 10 amino acids preceding the toxin region. Electrophysiological experiments, carried out on mouse pancreatic B-cells, showed that glacontryphan-M blocks L-type voltage-gated calcium ion channel activity in a calciumdependent manner. Glacontryphan-M is the first contryphan reported to modulate the activity of L-type calcium ion channels.

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“…The toxic effects of δ-conotoxins were subsequently attributed to a delay of VGSC inactivation in molluscan neurons (Fainzilber et al 1991) through what appears to be a new site on the VGSC (Fainzilber et al 1994). Interestingly, this site has been shown to overlap the μO-conotoxin binding site in rat brain (Ekberg et al 2006), which is not surpising given their similar hydrophobicity and related structures.…”

Section: -Conotoxinsmentioning

confidence: 99%

Developmental Biology of Neoplastic Growth

Macieira‐Coelho¹

2005

Progress in Molecular and Subcellular Biology

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Mollusc‐specific toxins from the venom of Conus textile neovicarius

Cited by 96 publications

References 29 publications

λ-Conotoxins, a New Family of Conotoxins with Unique Disulfide Pattern and Protein Folding

λ-Conotoxins, a New Family of Conotoxins with Unique Disulfide Pattern and Protein Folding

The First γ-Carboxyglutamic Acid-containing Contryphan

Developmental Biology of Neoplastic Growth

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