Kbot1, a three disulfide bridges toxin from Buthus occitanus tunetanus venom highly active on both SK and Kv channels.
On attempts to identify toxins showing original profile of activity among K+ channels, we purified Kbot1, a scorpion toxin that blocks Kv1 and SK potassium channels. With 28 amino-acid residues, Kbot1 is the shortest toxin sequenced in Buthus occitanus scorpion. It is linked by three disulfide bridges and its primary structure is 93% identical to that of BmP02 isolated from the venom of the Chinese scorpion Buthus martensi Karsch [Eur. J. Biochem. 245 (1996) 457]. Kbot1 exhibited a low neurotoxicity in mice after intracerebroventricular injection (LD50 approximately or = 0.8 microg per mouse). It competes with iodinated apamin for its rat brain synaptosomal membrane-binding site (IC50 of 20 nM). Despite 30% sequence identity between Kbot1 and ChTX, competitive experiments on the [125I] charybdotoxin, show that Kbot1 inhibits its binding to its rat brain synaptosomes with IC50 of 10 nM. This result was supported by electrophysiological experiments on cloned voltage-dependent K+ channels from rat brain, expressed in Xenopus oocytes. Kbot1 blocks Kv1.1, Kv1.2 and Kv1.3 currents with IC50 of 145, 2.5 and 15 nM, respectively. Based on these data, Kbot1 may be considered as the first member of subfamily 9 of scorpion toxins [Trends Pharmacol. Sci. 20 (1999) 444], highly active on both Kv and SK channels.
Mahjoubi-Boubaker
Basma
B
Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, B.P. 74, 1002 Tunis-Belvédère, Tunisia.
Crest
Marcel
M
Khalifa
Rym Ben
RB
El Ayeb
Mohamed
M
Kharrat
Riadh
R
D000595:Amino Acid Sequence; D000818:Animals; D018999:Charybdotoxin; D004220:Disulfides / Q000737:chemistry*; D015870:Gene Expression; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D012605:Scorpions / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014118:Toxins, Biological / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity*; D014981:Xenopus
D004220:Disulfides; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D014118:Toxins, Biological; D018999:Charybdotoxin