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.
Synthesis, solution structure, and phylum selectivity of a spider delta-toxin that slows inactivation of specific voltage-gated sodium channel subtypes.
Yamaji N
,
Little MJ
,
Nishio H
,
Billen B
,
Villegas E
,
Nishiuchi Y
,
Tytgat J
,
Nicholson GM
,
Corzo G
.
???displayArticle.abstract???
Magi 4, now renamed delta-hexatoxin-Mg1a, is a 43-residue neurotoxic peptide from the venom of the hexathelid Japanese funnel-web spider (Macrothele gigas) with homology to delta-hexatoxins from Australian funnel-web spiders. It binds with high affinity to receptor site 3 on insect voltage-gated sodium (Na(V)) channels but, unlike delta-hexatoxins, does not compete for the related site 3 in rat brain despite being previously shown to be lethal by intracranial injection. To elucidate differences in Na(V) channel selectivity, we have undertaken the first characterization of a peptide toxin on a broad range of mammalian and insect Na(V) channel subtypes showing that delta-hexatoxin-Mg1a selectively slows channel inactivation of mammalian Na(V)1.1, Na(V)1.3, and Na(V)1.6 but more importantly shows higher affinity for insect Na(V)1 (para) channels. Consequently, delta-hexatoxin-Mg1a induces tonic repetitive firing of nerve impulses in insect neurons accompanied by plateau potentials. In addition, we have chemically synthesized and folded delta-hexatoxin-Mg1a, ascertained the bonding pattern of the four disulfides, and determined its three-dimensional solution structure using NMR spectroscopy. Despite modest sequence homology, we show that key residues important for the activity of scorpion alpha-toxins and delta-hexatoxins are distributed in a topologically similar manner in delta-hexatoxin-Mg1a. However, subtle differences in the toxin surfaces are important for the novel selectivity of delta-hexatoxin-Mg1a for certain mammalian and insect Na(V) channel subtypes. As such, delta-hexatoxin-Mg1a provides us with a specific tool with which to study channel structure and function and determinants for phylum- and tissue-specific activity.
Birinyi-Strachan,
Neuroprotectant effects of iso-osmolar D-mannitol to prevent Pacific ciguatoxin-1 induced alterations in neuronal excitability: a comparison with other osmotic agents and free radical scavengers.
2005, Pubmed
Birinyi-Strachan,
Neuroprotectant effects of iso-osmolar D-mannitol to prevent Pacific ciguatoxin-1 induced alterations in neuronal excitability: a comparison with other osmotic agents and free radical scavengers.
2005,
Pubmed
Black,
Spinal sensory neurons express multiple sodium channel alpha-subunit mRNAs.
1996,
Pubmed
Bosmans,
Four novel tarantula toxins as selective modulators of voltage-gated sodium channel subtypes.
2006,
Pubmed
,
Xenbase
Böhm,
Quantitative analysis of protein far UV circular dichroism spectra by neural networks.
1992,
Pubmed
Catterall,
Cellular and molecular biology of voltage-gated sodium channels.
1992,
Pubmed
Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
Pubmed
Cestèle,
Molecular mechanisms of neurotoxin action on voltage-gated sodium channels.
2000,
Pubmed
Cierpicki,
NMR solution structure of Apis mellifera chymotrypsin/cathepsin G inhibitor-1 (AMCI-1): structural similarity with Ascaris protease inhibitors.
2000,
Pubmed
Corzo,
Distinct primary structures of the major peptide toxins from the venom of the spider Macrothele gigas that bind to sites 3 and 4 in the sodium channel.
2003,
Pubmed
Fernandez,
Membrane patches and whole-cell membranes: a comparison of electrical properties in rat clonal pituitary (GH3) cells.
1984,
Pubmed
Fletcher,
The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel.
1997,
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
Gilles,
Variations in receptor site-3 on rat brain and insect sodium channels highlighted by binding of a funnel-web spider delta-atracotoxin.
2002,
Pubmed
Gilles,
A scorpion alpha-like toxin that is active on insects and mammals reveals an unexpected specificity and distribution of sodium channel subtypes in rat brain neurons.
1999,
Pubmed
,
Xenbase
Gordon,
The differential preference of scorpion alpha-toxins for insect or mammalian sodium channels: implications for improved insect control.
2007,
Pubmed
Gordon,
Tissue-specific expression of the RI and RII sodium channel subtypes.
1987,
Pubmed
Gordon,
A new approach to insect-pest control--combination of neurotoxins interacting with voltage sensitive sodium channels to increase selectivity and specificity.
1997,
Pubmed
Grolleau,
Dorsal unpaired median neurones in the insect central nervous system: towards a better understanding of the ionic mechanisms underlying spontaneous electrical activity.
2000,
Pubmed
Grolleau,
Electrophysiological analysis of the neurotoxic action of a funnel-web spider toxin, delta-atracotoxin-HV1a, on insect voltage-gated Na+ channels.
2001,
Pubmed
Guex,
SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling.
1997,
Pubmed
Gunning,
Isolation of delta-missulenatoxin-Mb1a, the major vertebrate-active spider delta-toxin from the venom of Missulena bradleyi (Actinopodidae).
2003,
Pubmed
Gunning,
The Janus-faced atracotoxins are specific blockers of invertebrate K(Ca) channels.
2008,
Pubmed
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Housset,
Crystal structure of toxin II from the scorpion Androctonus australis Hector refined at 1.3 A resolution.
1994,
Pubmed
Hutchinson,
A revised set of potentials for beta-turn formation in proteins.
1994,
Pubmed
Karbat,
Molecular basis of the high insecticidal potency of scorpion alpha-toxins.
2004,
Pubmed
Karbat,
The unique pharmacology of the scorpion alpha-like toxin Lqh3 is associated with its flexible C-tail.
2007,
Pubmed
King,
A rational nomenclature for naming peptide toxins from spiders and other venomous animals.
2008,
Pubmed
King,
Peptide toxins that selectively target insect Na(V) and Ca(V) channels.
2008,
Pubmed
Koradi,
MOLMOL: a program for display and analysis of macromolecular structures.
1996,
Pubmed
Krimm,
NMR structures and activity of a novel alpha-like toxin from the scorpion Leiurus quinquestriatus hebraeus.
1999,
Pubmed
Laskowski,
AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR.
1996,
Pubmed
Leipold,
Combinatorial interaction of scorpion toxins Lqh-2, Lqh-3, and LqhalphaIT with sodium channel receptor sites-3.
2004,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
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
Little,
Delta-atracotoxins from Australian funnel-web spiders compete with scorpion alpha-toxin binding on both rat brain and insect sodium channels.
1998,
Pubmed
Maertens,
Potent modulation of the voltage-gated sodium channel Nav1.7 by OD1, a toxin from the scorpion Odonthobuthus doriae.
2006,
Pubmed
,
Xenbase
Nicholson,
Differential blockade of neuronal voltage-gated Na(+) and K(+) channels by antidepressant drugs.
2002,
Pubmed
Nicholson,
Structure and function of delta-atracotoxins: lethal neurotoxins targeting the voltage-gated sodium channel.
2004,
Pubmed
Nicholson,
Modification of sodium channel gating and kinetics by versutoxin from the Australian funnel-web spider Hadronyche versuta.
1994,
Pubmed
Nicholson,
Characterisation of the effects of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, on sodium channel activation and inactivation.
1998,
Pubmed
Oliveira,
Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels: unexpected contributions from differences in the IV/S3-S4 outer loop.
2004,
Pubmed
Ostman,
GTP up-regulated persistent Na+ current and enhanced nociceptor excitability require NaV1.9.
2008,
Pubmed
Pallaghy,
A common structural motif incorporating a cystine knot and a triple-stranded beta-sheet in toxic and inhibitory polypeptides.
1994,
Pubmed
Pallaghy,
Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus.
1997,
Pubmed
Pardi,
Protein conformation and proton nuclear-magnetic-resonance chemical shifts.
1983,
Pubmed
Rash,
Neurotoxic activity of venom from the Australian eastern mouse spider (Missulena bradleyi) involves modulation of sodium channel gating.
2000,
Pubmed
Roy,
Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons.
1992,
Pubmed
Schreibmayer,
A mechanistic interpretation of the action of toxin II from Anemonia sulcata on the cardiac sodium channel.
1987,
Pubmed
Schwieters,
The Xplor-NIH NMR molecular structure determination package.
2003,
Pubmed
Sheumack,
Complete amino acid sequence of a new type of lethal neurotoxin from the venom of the funnel-web spider Atrax robustus.
1985,
Pubmed
Strichartz,
Rapid voltage-dependent dissociation of scorpion alpha-toxins coupled to Na channel inactivation in amphibian myelinated nerves.
1986,
Pubmed
Szeto,
Isolation and pharmacological characterisation of delta-atracotoxin-Hv1b, a vertebrate-selective sodium channel toxin.
2000,
Pubmed
Tugarinov,
Solution structures of a highly insecticidal recombinant scorpion alpha-toxin and a mutant with increased activity.
1997,
Pubmed
Waxman,
Diverse functions and dynamic expression of neuronal sodium channels.
2002,
Pubmed
Wilmot,
Beta-turns and their distortions: a proposed new nomenclature.
1990,
Pubmed
