Holocyclotoxin-1, a cystine knot toxin from Ixodes holocyclus

Vink, Simone, Daly, Norelle, Steen, Natalie, Craik, David J., and Alewood, Paul F. (2014) Holocyclotoxin-1, a cystine knot toxin from Ixodes holocyclus. Toxicon, 90. pp. 308-317.

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In the past 100 years minimal venom research has focused on ticks despite several species possessing a highly paralytic and lethal venom cocktail of proteinaceous molecules. The saliva of the Australian paralysis tick, Ixodes holocyclus, has been responsible for 20 human fatalities from 1900 to 1945, and up to 100,000 domestic animal fatalities annually. In the last 50 years, research on this tick has focused on identifying the neurotoxins present in the saliva and in the last ten years the sequence of a potential neurotoxin, HT-1, has been determined. In this study we chemically synthesised HT-1 using Boc-chemistry in combination with native chemical ligation. Following successful oxidative folding, we determined the three-dimensional structure of HT-1 by NMR spectroscopy and found a novel structural fold with three of the four disulfide bonds comprising the inhibitory cystine knot (ICK) motif. The fourth disulfide bond connects the second loop to the N-terminal, which decreases the flexibility of the structure.

Item ID: 36372
Item Type: Article (Research - C1)
ISSN: 1879-3150
Keywords: Ixodes holocyclus; holocyclotoxin-1; paralysis tick; ICK motif; SPPS; native chemical ligation
Funders: National Health and Medical Research Council (NHMRC), Australian Research Council (ARC)
Projects and Grants: NHMRC Senior Principal Research Fellowship APP1026501, ARC FF110100226, NHMRC Program Grant (351446)
Date Deposited: 03 Dec 2014 04:05
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060101 Analytical Biochemistry @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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