Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biochem J
2007 Aug 15;4061:41-8. doi: 10.1042/BJ20070233.
Show Gene links
Show Anatomy links
Molecular analysis of the sea anemone toxin Av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated Na+ channels.
Moran Y
,
Kahn R
,
Cohen L
,
Gur M
,
Karbat I
,
Gordon D
,
Gurevitz M
.
???displayArticle.abstract???
Av3 is a short peptide toxin from the sea anemone Anemonia viridis shown to be active on crustaceans and inactive on mammals. It inhibits inactivation of Na(v)s (voltage-gated Na+ channels) like the structurally dissimilar scorpion alpha-toxins and type I sea anemone toxins that bind to receptor site-3. To examine the potency and mode of interaction of Av3 with insect Na(v)s, we established a system for its expression, mutagenized it throughout, and analysed it in toxicity, binding and electrophysiological assays. The recombinant Av3 was found to be highly toxic to blowfly larvae (ED50=2.65+/-0.46 pmol/100 mg), to compete well with the site-3 toxin LqhalphaIT (from the scorpion Leiurus quinquestriatus) on binding to cockroach neuronal membranes (K(i)=21.4+/-7.1 nM), and to inhibit the inactivation of Drosophila melanogaster channel, DmNa(v)1, but not that of mammalian Na(v)s expressed in Xenopus oocytes. Moreover, like other site-3 toxins, the activity of Av3 was synergically enhanced by ligands of receptor site-4 (e.g. scorpion beta-toxins). The bioactive surface of Av3 was found to consist mainly of aromatic residues and did not resemble any of the bioactive surfaces of other site-3 toxins. These analyses have portrayed a toxin that might interact with receptor site-3 in a different fashion compared with other ligands of this site. This assumption was corroborated by a D1701R mutation in DmNa(v)1, which has been shown to abolish the activity of all other site-3 ligands, except Av3. All in all, the present study provides further evidence for the heterogeneity of receptor site-3, and raises Av3 as a unique model for design of selective anti-insect compounds.
Arnon,
BjalphaIT: a novel scorpion alpha-toxin selective for insects--unique pharmacological tool.
2005, Pubmed,
Xenbase
Arnon,
BjalphaIT: a novel scorpion alpha-toxin selective for insects--unique pharmacological tool.
2005,
Pubmed
,
Xenbase
Benzinger,
A specific interaction between the cardiac sodium channel and site-3 toxin anthopleurin B.
1998,
Pubmed
Blumenthal,
Voltage-gated sodium channel toxins: poisons, probes, and future promise.
2003,
Pubmed
Bosmans,
The sea anemone Bunodosoma granulifera contains surprisingly efficacious and potent insect-selective toxins.
2002,
Pubmed
,
Xenbase
Bosmans,
Voltage-gated sodium channel modulation by scorpion alpha-toxins.
2007,
Pubmed
Béress,
Isolation and characterisation of three polypeptides with neurotoxic activity from Anemonia sulcata.
1975,
Pubmed
Catterall,
Sea anemone toxin and scorpion toxin share a common receptor site associated with the action potential sodium ionophore.
1978,
Pubmed
Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
Pubmed
Cohen,
Allosteric interactions between scorpion toxin receptor sites on voltage-gated Na channels imply a novel role for weakly active components in arthropod venom.
2006,
Pubmed
Froy,
The putative bioactive surface of insect-selective scorpion excitatory neurotoxins.
1999,
Pubmed
Gilles,
Structural implications on the interaction of scorpion alpha-like toxins with the sodium channel receptor site inferred from toxin iodination and pH-dependent binding.
2000,
Pubmed
Gordon,
Scorpion toxins affecting sodium current inactivation bind to distinct homologous receptor sites on rat brain and insect sodium channels.
1996,
Pubmed
Gordon,
The differential preference of scorpion alpha-toxins for insect or mammalian sodium channels: implications for improved insect control.
2007,
Pubmed
Gordon,
Binding of an alpha scorpion toxin to insect sodium channels is not dependent on membrane potential.
1993,
Pubmed
Greenfield,
Methods to estimate the conformation of proteins and polypeptides from circular dichroism data.
1996,
Pubmed
Guo,
Partial purification of human parathyroid hormone 1-84 as a thioredoxin fusion form in recombinant Escherichia coli by thermoosmotic shock.
2006,
Pubmed
Gurevitz,
The insecticidal potential of scorpion beta-toxins.
2007,
Pubmed
Hartung,
Anemonia sulcata toxins modify activation and inactivation of Na+ currents in a crayfish neurone.
1985,
Pubmed
Honma,
Peptide toxins in sea anemones: structural and functional aspects.
2006,
Pubmed
Karbat,
Conversion of a scorpion toxin agonist into an antagonist highlights an acidic residue involved in voltage sensor trapping during activation of neuronal Na+ channels.
2004,
Pubmed
Karbat,
Molecular basis of the high insecticidal potency of scorpion alpha-toxins.
2004,
Pubmed
Leipold,
Combinatorial interaction of scorpion toxins Lqh-2, Lqh-3, and LqhalphaIT with sodium channel receptor sites-3.
2004,
Pubmed
Little,
delta-Atracotoxins from australian funnel-web spiders compete with scorpion alpha-toxin binding but differentially modulate alkaloid toxin activation of voltage-gated sodium channels.
1998,
Pubmed
Loret,
Positively charged amino acid residues located similarly in sea anemone and scorpion toxins.
1994,
Pubmed
Manoleras,
Three-dimensional structure in solution of neurotoxin III from the sea anemone Anemonia sulcata.
1994,
Pubmed
Martinez,
Toxin III from Anemonia sulcata: primary structure.
1977,
Pubmed
Moran,
Expression and mutagenesis of the sea anemone toxin Av2 reveals key amino acid residues important for activity on voltage-gated sodium channels.
2006,
Pubmed
,
Xenbase
Norton,
Structure and structure-function relationships of sea anemone proteins that interact with the sodium channel.
1991,
Pubmed
Rochat,
Radioiodination of scorpion and snake toxins.
1977,
Pubmed
Rogers,
Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit.
1996,
Pubmed
Salceda,
The sea anemone toxins BgII and BgIII prolong the inactivation time course of the tetrodotoxin-sensitive sodium current in rat dorsal root ganglion neurons.
2002,
Pubmed
Schweitz,
Lethal potency in mice of toxins from scorpion, sea anemone, snake and bee venoms following intraperitoneal and intracisternal injection.
1984,
Pubmed
Schweitz,
Purification and pharmacological properties of eight sea anemone toxins from Anemonia sulcata, Anthopleura xanthogrammica, Stoichactis giganteus, and Actinodendron plumosum.
1981,
Pubmed
Shichor,
Domain 2 of Drosophila para voltage-gated sodium channel confers insect properties to a rat brain channel.
2002,
Pubmed
,
Xenbase
Tugarinov,
Solution structures of a highly insecticidal recombinant scorpion alpha-toxin and a mutant with increased activity.
1997,
Pubmed
Ulbricht,
Sodium channel inactivation: molecular determinants and modulation.
2005,
Pubmed
Vass,
Vibrational spectroscopic detection of beta- and gamma-turns in synthetic and natural peptides and proteins.
2003,
Pubmed
Warmke,
Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology.
1997,
Pubmed
,
Xenbase
Zilberberg,
Functional expression and genetic alteration of an alpha scorpion neurotoxin.
1996,
Pubmed
de Lima,
The toxin Tx4(6-1) from the spider Phoneutria nigriventer slows down Na(+) current inactivation in insect CNS via binding to receptor site 3.
2002,
Pubmed
