期刊
FASEB JOURNAL
卷 23, 期 2, 页码 534-545出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.08-113555
关键词
postsynaptic neurotoxin; acetylcholine receptor; neuromuscular junction; snake venom
资金
- Biomedical Research Council (BMRC), Agency for Science and Technology, Singapore [01/1/21/18/072, 07/1/21/19/490, 06/1/33/19/481]
- U.S. Geological Service Biological Resources Division [00CRAG0014]
A novel heterodimeric three-finger neurotoxin, irditoxin, was isolated from venom of the brown treesnake Boiga irregularis (Colubridae). Irditoxin subunit amino acid sequences were determined by Edman degradation and cDNA sequencing. The crystal structure revealed two subunits with a three-finger protein fold, typical for nonconventional toxins such as denmotoxin, bucandin, and candoxin. This is the first colubrid three-finger toxin dimer, covalently connected via an interchain disulfide bond. Irditoxin showed taxon-specific lethality toward birds and lizards and was nontoxic toward mice. It produced a potent neuromuscular blockade at the avian neuromuscular junction (IC50 = 10 nM), comparable to alpha-bungarotoxin, but was three orders of magnitude less effective at the mammalian neuromuscular junction. Covalently linked heterodimeric three-finger toxins found in colubrid venoms constitute a new class of venom peptides, which may be a useful source of new neurobiology probes and therapeutic leads. - Pawlak, J., Mackessy, S. P., Sixberry, N. M., Stura, E. A., Le Du, M. H., Menez, R., Foo, C. S., Menez, A., Nirthanan, S., Kini, R. M. Irditoxin, a novel covalently linked heterodimeric three-finger toxin with high taxon-specific neurotoxicity. FASEB J. 23, 534-545 (2009)
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