The cystine knot is responsible for the exceptional stability of the insecticidal spider toxin ω-Hexatoxin-Hv1a

Volker Herzig; G F King

doi:10.3390/toxins7104366

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The cystine knot is responsible for the exceptional stability of the insecticidal spider toxin ω-Hexatoxin-Hv1a

Journal article

Open access

Peer reviewed

The cystine knot is responsible for the exceptional stability of the insecticidal spider toxin ω-Hexatoxin-Hv1a

Volker Herzig and G F King

Toxins, Vol.7(10), pp.4366-4380

2015

DOI: https://doi.org/10.3390/toxins7104366

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Abstract

inhibitor cystine knot

physicochemical stability

spider toxin

insecticidal toxin

ω-hexatoxin-Hv1a

thermal stability

proteolytic degradation

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.

Details

Title: The cystine knot is responsible for the exceptional stability of the insecticidal spider toxin ω-Hexatoxin-Hv1a
Authors: Volker Herzig (Author) - University of Queensland
G F King (Author) - University of Queensland
Publication details: Toxins, Vol.7(10), pp.4366-4380
Publisher: MDPI AG
Date published: 2015
DOI: 10.3390/toxins7104366
ISSN: 2072-6651
Copyright note: Copyright © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
Organisation Unit: School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99450961602621
Output Type: Journal article

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