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Biochem J
2003 Nov 01;375Pt 3:551-60. doi: 10.1042/BJ20030688.
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Characterization of Amm VIII from Androctonus mauretanicus mauretanicus: a new scorpion toxin that discriminates between neuronal and skeletal sodium channels.
Alami M
,
Vacher H
,
Bosmans F
,
Devaux C
,
Rosso JP
,
Bougis PE
,
Tytgat J
,
Darbon H
,
Martin-Eauclaire MF
.
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The venom of the scorpion Androctonus mauretanicus mauretanicus was screened by use of a specific serum directed against AaH II, the scorpion alpha-toxin of reference, with the aim of identifying new analogues. This led to the isolation of Amm VIII (7382.57 Da), which gave a highly positive response in ELISA, but was totally devoid of toxicity when injected subcutaneously into mice. In voltage-clamp experiments with rat brain type II Na+ channel rNa(v)1.2 or rat skeletal muscle Na+ channel rNa(v)1.4, expressed in Xenopus oocytes, the EC50 values of the toxin-induced slowing of inactivation were: 29+/-5 and 416+/-14 nM respectively for AmmVIII and 2.6+/-0.3 nM and 2.2+/-0.2 nM, respectively, for AaH II interactions. Accordingly, Amm VIII clearly discriminates neuronal versus muscular Na+ channel. The Amm VIII cDNA was amplified from a venom gland cDNA library and its oligonucleotide sequence determined. It shows 87% sequence homology with AaH II, but carries an unusual extension at its C-terminal end, consisting of an additional Asp due to a point mutation in the cDNA penultimate codon. We hypothesized that this extra amino acid residue could induce steric hindrance and dramatically reduce recognition of the target by Amm VIII. We constructed a model of Amm VIII based on the X-ray structure of AaH II to clarify this point. Molecular modelling showed that this C-terminal extension does not lead to an overall conformational change in Amm VIII, but drastically modifies the charge repartition and, consequently, the electrostatic dipole moment of the molecule. At last, liquid-phase radioimmunassays with poly- and monoclonal anti-(AaH II) antibodies showed the loss of conformational epitopes between AaH II and Amm VIII.
Alami,
Characterisation of the gene encoding the alpha-toxin Amm V from the scorpion Androctonus mauretanicus mauretanicus.
2001, Pubmed
Alami,
Characterisation of the gene encoding the alpha-toxin Amm V from the scorpion Androctonus mauretanicus mauretanicus.
2001,
Pubmed
Bahraoui,
Immunochemistry of scorpion alpha-toxins: study with synthetic peptides of the antigenicity of four regions of toxin II of Androctonus australis Hector.
1986,
Pubmed
Bahraoui,
Monoclonal antibodies to scorpion toxins. Characterization and molecular mechanisms of neutralization.
1988,
Pubmed
Benzinger,
A specific interaction between the cardiac sodium channel and site-3 toxin anthopleurin B.
1998,
Pubmed
Bougis,
Precursors of Androctonus australis scorpion neurotoxins. Structures of precursors, processing outcomes, and expression of a functional recombinant toxin II.
1989,
Pubmed
Catterall,
Cellular and molecular biology of voltage-gated sodium channels.
1992,
Pubmed
Cestèle,
Scorpion alpha-like toxins, toxic to both mammals and insects, differentially interact with receptor site 3 on voltage-gated sodium channels in mammals and insects.
1999,
Pubmed
Cestèle,
Molecular mechanisms of neurotoxin action on voltage-gated sodium channels.
2000,
Pubmed
Chen,
Differential sensitivity of sodium channels from the central and peripheral nervous system to the scorpion toxins Lqh-2 and Lqh-3.
2002,
Pubmed
Crest,
Kaliotoxin, a novel peptidyl inhibitor of neuronal BK-type Ca(2+)-activated K+ channels characterized from Androctonus mauretanicus mauretanicus venom.
1992,
Pubmed
Darbon,
Alpha-scorpion neurotoxin derivatives suitable as potential markers of sodium channels. Preparation and characterization.
1983,
Pubmed
Devaux,
Monoclonal antibodies neutralizing the toxin II from Androctonus australis hector scorpion venom: usefulness of a synthetic, non-toxic analog.
1997,
Pubmed
El Ayeb,
Immunochemistry of scorpion alpha-toxins: antigenic homologies checked with radioimmunoassays (RIA).
1983,
Pubmed
Ferrat,
Structural basis for alpha-K toxin specificity for K+ channels revealed through the solution 1H NMR structures of two noxiustoxin-iberiotoxin chimeras.
2001,
Pubmed
Fontecilla-Camps,
Orthorhombic crystals and three-dimensional structure of the potent toxin II from the scorpion Androctonus australis Hector.
1988,
Pubmed
Froy,
The putative bioactive surface of insect-selective scorpion excitatory neurotoxins.
1999,
Pubmed
Gellens,
Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel.
1992,
Pubmed
,
Xenbase
Gilles,
Scorpion alpha and alpha-like toxins differentially interact with sodium channels in mammalian CNS and periphery.
2000,
Pubmed
Gordon,
Scorpion toxins affecting sodium current inactivation bind to distinct homologous receptor sites on rat brain and insect sodium channels.
1996,
Pubmed
Granier,
The antigenic structure of a scorpion toxin.
1989,
Pubmed
Hamon,
Characterization of scorpion alpha-like toxin group using two new toxins from the scorpion Leiurus quinquestriatus hebraeus.
2002,
Pubmed
,
Xenbase
Hassani,
Aah VI, a novel, N-glycosylated anti-insect toxin from Androctonus australis hector scorpion venom: isolation, characterisation, and glycan structure determination.
1999,
Pubmed
Kharrat,
Structure/activity relationships of scorpion alpha-toxins. Multiple residues contribute to the interaction with receptors.
1989,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Martin,
Large scale purification of toxins from the venom of the scorpion Androctonus australis Hector.
1986,
Pubmed
Noda,
Existence of distinct sodium channel messenger RNAs in rat brain.
,
Pubmed
Pimenta,
Moving pieces in a proteomic puzzle: mass fingerprinting of toxic fractions from the venom of Tityus serrulatus (Scorpiones, Buthidae).
2001,
Pubmed
Pinheiro,
Structural analysis of Tityus serrulatus Ts1 neurotoxin at atomic resolution: insights into interactions with Na+ channels.
2003,
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
Romi-Lebrun,
Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels.
1997,
Pubmed
,
Xenbase
Rosso,
Characterization of ten proteins from the venom of the Moroccan scorpion Androctonus mauretanicus mauretanicus, six of which are toxic to the mouse.
1985,
Pubmed
Srairi-Abid,
Purification, characterization and molecular modelling of two toxin-like proteins from the Androctonus australis Hector venom.
2000,
Pubmed
Thomsen,
Localization of the receptor site for alpha-scorpion toxins by antibody mapping: implications for sodium channel topology.
1989,
Pubmed
Trimmer,
Primary structure and functional expression of a mammalian skeletal muscle sodium channel.
1989,
Pubmed
,
Xenbase
Zerrouk,
Analysis by high-performance liquid chromatography of Androctonus mauretanicus mauretanicus (black scorpion) venom.
1991,
Pubmed
Zilberberg,
Identification of structural elements of a scorpion alpha-neurotoxin important for receptor site recognition.
1997,
Pubmed
Zilberberg,
Functional expression and genetic alteration of an alpha scorpion neurotoxin.
1996,
Pubmed
