Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif

Smith, Jennifer J., Hill, Justine M., Little, Michelle J., Nicholson, Graham M., King, Glenn F. and Alewood, Paul F. (2011) Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif. Proceedings of the National Academy of Sciences of the United States of America, 108 26: 10478-10483. doi:10.1073/pnas.1103501108


Author Smith, Jennifer J.
Hill, Justine M.
Little, Michelle J.
Nicholson, Graham M.
King, Glenn F.
Alewood, Paul F.
Title Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2011-06-13
Year available 2011
Sub-type Article (original research)
DOI 10.1073/pnas.1103501108
Open Access Status Not Open Access
Volume 108
Issue 26
Start page 10478
End page 10483
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Abstract The three-disulfide inhibitor cystine knot (ICK) motif is a fold common to venom peptides from spiders, scorpions, and aquatic cone snails. Over a decade ago it was proposed that the ICK motif is an elaboration of an ancestral two-disulfide fold coined the disulfide-directed beta-hairpin (DDH). Here we report the isolation, characterization, and structure of a novel toxin [U(1)-liotoxin-Lw1a (U(1)-LITX-Lw1a)] from the venom of the scorpion Liocheles waigiensis that is the first example of a native peptide that adopts the DDH fold. U(1)-LITX-Lw1a not only represents the discovery of a missing link in venom protein evolution, it is the first member of a fourth structural fold to be adopted by scorpion-venom peptides. Additionally, we show that U(1)-LITX-Lw1a has potent insecticidal activity across a broad range of insect pest species, thereby providing a unique structural scaffold for bioinsecticide development.
Formatted abstract
The three-disulfide inhibitor cystine knot (ICK) motif is a fold common to venom peptides from spiders, scorpions, and aquatic cone snails. Over a decade ago it was proposed that the ICK motif is an elaboration of an ancestral two-disulfide fold coined the disulfide-directed β-hairpin (DDH). Here we report the isolation, characterization, and structure of a novel toxin [U1-liotoxin-Lw1a (U1-LITX-Lw1a)] from the venom of the scorpion Liocheles waigiensis that is the first example of a native peptide that adopts the DDH fold. U1-LITX-Lw1a not only represents the discovery of a missing link in venom protein evolution, it is the first member of a fourth structural fold to be adopted by scorpion-venom peptides. Additionally, we show that U1-LITX-Lw1a has potent insecticidal activity across a broad range of insect pest species, thereby providing a unique structural scaffold for bioinsecticide development.
Keyword Molecular evolution
NMR
Protein structure
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP0774245
351446
Institutional Status UQ

 
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Created: Mon, 03 Oct 2011, 22:53:15 EST by Dr Justine Hill on behalf of Institute for Molecular Bioscience