Dc1a contains two β-sheets and one β-hairpin loop whereas the sheets are held together by four disulphide bonds. Three of these four disulphide bonds form a classical cysteine knot region (ICK). ICK region is common in spider toxins and provides chemical, thermal and biological stability to the protein. Although this region is evolutionary conserved in the spiders family, it has remarkable differences with other ICK-like proteins. One of the special characteristics is that Dc1a contains an additional disulphide bond that links cysteine 42 with cysteine 45 and stabilizes the serine-rich hairpin loop. Another feature is a unique three-standard antiparallel β-sheet in the amino-terminal region which is formed by an unusually large loop between cysteine 26 and cysteine 40. This difference in structure creates a spatial separation between the ICK domain and the rest of the protein, leaving the charged residues more exposed. However, clusters of hydrophobic residues that could potentially interact with lipid bilayers have not been found.Bende, N. S., Dziemborowicz, S., Mobli, M., Herzig, V., Gilchrist, J., Wagner, J., ... & Bosmans, F. (2014). A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a. Nature Communications, 5, 4350.
