TAILIEUCHUNG - Báo cáo khoa học: An ‘Old World’ scorpion b-toxin that recognizes both insect and mammalian sodium channels A possible link towards diversification of b-toxins

Scorpion toxins that affect sodium channel (NaCh) gating in excitable cells are divided into a-andb-classes. Whereas a-toxinshavebeen found inscorpions throughout theworld, anti-mammalianb-toxins have been assigned, thus far, to New World scorpions while anti-insect selective b-toxins (depressant and excitatory) have been described only in the Old World . 2 This distribution suggested that diversification ofb-toxins into distinct pharmacological groups occurred after the separation of the continents, 150 million years ago | Eur. J. Biochem. 270 2663-2670 2003 FEBS 2003 doi An Old World scorpion b-toxin that recognizes both insect and mammalian sodium channels A possible link towards diversification of b-toxins Dalia Gordon1 Nitza Ilan1 6. Noam Zilberbera2. Nicolas Gilles3 Daniel Urbach1 Lior Cohen1 Izhar Karbat1 Oren Froy1 Ariel Gaathon4 Roland G. Kallen5 Morris Benveniste6 and Michael Gurevitz1 1 Department of Plant Sciences George S. Wise Faculty of Life Sciences Tel-Aviv University Israel department of Life Sciences Ben-Gurion University Israel 3CEA Department dTngéniérie et d Etudes des Proteines France 4Bletterman Research Laboratory for Macromolecules The Hebrew University-Hadassah Medical School Jerusalem Israel 5Department of Biochemistry and Biophysics University of Pennsylvania School of Medicine Philadelphia PA USA department of Physiology and Pharmacology Sackler School of Medicine Tel-Aviv University Israel Scorpion toxins that affect sodium channel NaCh gating in excitable cells are divided into a- and b-classes. Whereas a-toxins have been found in scorpions throughout the world anti-mammalian b-toxins have been assigned thus far to New World scorpions while anti-insect selective b-toxins depressant and excitatory have been described only in the Old World . This distribution suggested that diversification of b-toxins into distinct pharmacological groups occurred after the separation of the continents 150 million years ago. We have characterized a unique toxin Lqhb1 from the Old World scorpion Leiurus quinquestriatus hebraeus that resembles in sequence and activity both New World b-toxins as well as Old World depressant toxins. Lqhb1 competes with apparent high affinity with anti-insect and anti-mammalian b-toxins for binding to cockroach and rat brain synaptosomes respectively. Surprisingly Lqhb1 also competes with an anti-mammalian a-toxin on binding to rat brain NaChs. Analysis of Lqhb1 effects on rat brain and Drosophila Para NaChs .

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