The insecticidal spider toxin SFI1 is a knottin peptide that blocks the pore of insect voltage-gated sodium channels via a large β-hairpin loop

Bende, Niraj S., Dziemborowicz, Slawomir, Herzig, Volker, Ramanujam, Venkatraman, Brown, Geoffrey W., Bosmans, Frank, Nicholson, Graham M., King, Glenn F. and Mobli, Mehdi (2015) The insecticidal spider toxin SFI1 is a knottin peptide that blocks the pore of insect voltage-gated sodium channels via a large β-hairpin loop. FEBS Journal, 282 5: 904-920. doi:10.1111/febs.13189


Author Bende, Niraj S.
Dziemborowicz, Slawomir
Herzig, Volker
Ramanujam, Venkatraman
Brown, Geoffrey W.
Bosmans, Frank
Nicholson, Graham M.
King, Glenn F.
Mobli, Mehdi
Title The insecticidal spider toxin SFI1 is a knottin peptide that blocks the pore of insect voltage-gated sodium channels via a large β-hairpin loop
Journal name FEBS Journal   Check publisher's open access policy
ISSN 1742-4658
1742-464X
Publication date 2015-03
Year available 2015
Sub-type Article (original research)
DOI 10.1111/febs.13189
Open Access Status
Volume 282
Issue 5
Start page 904
End page 920
Total pages 17
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2016
Language eng
Formatted abstract
Spider venoms contain a plethora of insecticidal peptides that act on neuronal ion channels and receptors. Because of their high specificity, potency and stability, these peptides have attracted much attention as potential environmentally friendly insecticides. Although many insecticidal spider venom peptides have been isolated, the molecular target, mode of action and structure of only a small minority have been explored. Sf1a, a 46-residue peptide isolated from the venom of the tube-web spider Segesteria florentina, is insecticidal to a wide range of insects, but nontoxic to vertebrates. In order to investigate its structure and mode of action, we developed an efficient bacterial expression system for the production of Sf1a. We determined a high-resolution solution structure of Sf1a using multidimensional 3D/4D NMR spectroscopy. This revealed that Sf1a is a knottin peptide with an unusually large β-hairpin loop that accounts for a third of the peptide length. This loop is delimited by a fourth disulfide bond that is not commonly found in knottin peptides. We showed, through mutagenesis, that this large loop is functionally critical for insecticidal activity. Sf1a was further shown to be a selective inhibitor of insect voltage-gated sodium channels, consistent with its ‘depressant’ paralytic phenotype in insects. However, in contrast to the majority of spider-derived sodium channel toxins that function as gating modifiers via interaction with one or more of the voltage-sensor domains, Sf1a appears to act as a pore blocker.
Keyword Disulfide-rich peptide
Heteronuclear NMR
Pore blocker
Spider toxin
Voltage-gated sodium channel
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
Centre for Advanced Imaging Publications
 
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