TY - JOUR
T1 - BjαIT
T2 - A novel scorpion α-toxin selective for insects - Unique pharmacological tool
AU - Arnon, Tal
AU - Potikha, Tamara
AU - Sher, Daniel
AU - Elazar, Menashe
AU - Mao, Wenfu
AU - Tal, Tzachy
AU - Bosmans, Frank
AU - Tytgat, Jan
AU - Ben-Arie, Nissim
AU - Zlotkin, Eliahu
N1 - Funding Information:
This study is supported by the committee of German–Israeli Cooperation in Biotechnology.
PY - 2005/3
Y1 - 2005/3
N2 - Long-chain neurotoxins derived from the venom of the Buthidae scorpions, which affect voltage-gated sodium channels (VGSCs) can be subdivided according to their toxicity to insects into insect-selective excitatory and depressant toxins (β-toxins) and the α-like toxins which affect both mammals and insects. In the present study by the aid of reverse-phase HPLC column chromatography, RT-PCR, cloning and various toxicity assays, a new insect selective toxin designated as BjαIT was isolated from the venom of the Judean Black Scorpion (Buthotus judaicus), and its full primary sequence was determined: MNYLVVICFALLLMTVVESGRDAYIADNLNCAYTCGSNSYCNTECTKNGAVSGYCQWLGKYGNACWCINLPDKVPI RIPGACR (leader sequence is underlined). Despite its lack of toxicity to mammals and potent toxicity to insects, BjαIT reveals an amino acid sequence and an inferred spatial arrangement that is characteristic of the well-known scorpion α-toxins highly toxic to mammals. BjαITs sharp distinction between insects and mammals was also revealed by its effect on sodium conductance of two cloned neuronal VGSCs heterloguously expressed in Xenopus laevis oocytes and assayed with the two-electrode voltage-clamp technique. BjαIT completely inhibits the inactivation process of the insect para/tipE VGSC at a concentration of 100 nM, in contrast to the rat brain Na v1.2/β1 which is resistant to the toxin. The above categorical distinction between mammal and insect VGSCs exhibited by BjαIT enables its employment in the clarification of the molecular basis of the animal group specificity of scorpion venom derived neurotoxic polypeptides and voltage-gated sodium channels.
AB - Long-chain neurotoxins derived from the venom of the Buthidae scorpions, which affect voltage-gated sodium channels (VGSCs) can be subdivided according to their toxicity to insects into insect-selective excitatory and depressant toxins (β-toxins) and the α-like toxins which affect both mammals and insects. In the present study by the aid of reverse-phase HPLC column chromatography, RT-PCR, cloning and various toxicity assays, a new insect selective toxin designated as BjαIT was isolated from the venom of the Judean Black Scorpion (Buthotus judaicus), and its full primary sequence was determined: MNYLVVICFALLLMTVVESGRDAYIADNLNCAYTCGSNSYCNTECTKNGAVSGYCQWLGKYGNACWCINLPDKVPI RIPGACR (leader sequence is underlined). Despite its lack of toxicity to mammals and potent toxicity to insects, BjαIT reveals an amino acid sequence and an inferred spatial arrangement that is characteristic of the well-known scorpion α-toxins highly toxic to mammals. BjαITs sharp distinction between insects and mammals was also revealed by its effect on sodium conductance of two cloned neuronal VGSCs heterloguously expressed in Xenopus laevis oocytes and assayed with the two-electrode voltage-clamp technique. BjαIT completely inhibits the inactivation process of the insect para/tipE VGSC at a concentration of 100 nM, in contrast to the rat brain Na v1.2/β1 which is resistant to the toxin. The above categorical distinction between mammal and insect VGSCs exhibited by BjαIT enables its employment in the clarification of the molecular basis of the animal group specificity of scorpion venom derived neurotoxic polypeptides and voltage-gated sodium channels.
KW - Alpha neurotoxins
KW - Black Judean Scorpion
KW - Insect selectivity
KW - Scorpion venom
KW - Voltage-Gated Sodium Channels
UR - http://www.scopus.com/inward/record.url?scp=19944431668&partnerID=8YFLogxK
U2 - 10.1016/j.ibmb.2004.11.005
DO - 10.1016/j.ibmb.2004.11.005
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 15705498
AN - SCOPUS:19944431668
SN - 0965-1748
VL - 35
SP - 187
EP - 195
JO - Insect Biochemistry and Molecular Biology
JF - Insect Biochemistry and Molecular Biology
IS - 3
ER -