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Toxins 2015, 7(10), 4366-4380; doi:10.3390/toxins7104366

The Cystine Knot Is Responsible for the Exceptional Stability of the Insecticidal Spider Toxin ω-Hexatoxin-Hv1a

Institute for Molecular Bioscience, The University of Queensland, St. Lucia QLD 4072, Australia
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Authors to whom correspondence should be addressed.
Academic Editor: Ren Lai
Received: 25 August 2015 / Revised: 14 October 2015 / Accepted: 21 October 2015 / Published: 26 October 2015
(This article belongs to the Special Issue Arthropod Venoms)
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Abstract

The inhibitor cystine knot (ICK) is an unusual three-disulfide architecture in which one of the disulfide bonds bisects a loop formed by the two other disulfide bridges and the intervening sections of the protein backbone. Peptides containing an ICK motif are frequently considered to have high levels of thermal, chemical and enzymatic stability due to cross-bracing provided by the disulfide bonds. Experimental studies supporting this contention are rare, in particular for spider-venom toxins, which represent the largest diversity of ICK peptides. We used ω-hexatoxin-Hv1a (Hv1a), an insecticidal toxin from the deadly Australian funnel-web spider, as a model system to examine the contribution of the cystine knot to the stability of ICK peptides. We show that Hv1a is highly stable when subjected to temperatures up to 75 °C, pH values as low as 1, and various organic solvents. Moreover, Hv1a was highly resistant to digestion by proteinase K and when incubated in insect hemolymph and human plasma. We demonstrate that the ICK motif is essential for the remarkable stability of Hv1a, with the peptide’s stability being dramatically reduced when the disulfide bonds are eliminated. Thus, this study demonstrates that the ICK motif significantly enhances the chemical and thermal stability of spider-venom peptides and provides them with a high level of protease resistance. This study also provides guidance to the conditions under which Hv1a could be stored and deployed as a bioinsecticide. View Full-Text
Keywords: inhibitor cystine knot; physicochemical stability; spider toxin; insecticidal toxin; ω-hexatoxin-Hv1a; thermal stability; proteolytic degradation inhibitor cystine knot; physicochemical stability; spider toxin; insecticidal toxin; ω-hexatoxin-Hv1a; thermal stability; proteolytic degradation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Herzig, V.; King, G.F. The Cystine Knot Is Responsible for the Exceptional Stability of the Insecticidal Spider Toxin ω-Hexatoxin-Hv1a. Toxins 2015, 7, 4366-4380.

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