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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

(2015) FEBS JOURNAL. 282(5). p.904-920
Author
Organization
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 beta-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.
Keywords
disulfide-rich peptide, heteronuclear NMR, pore blocker, spider toxin, voltage-gated sodium channel, FUNNEL-WEB SPIDERS, MAXIMUM-ENTROPY RECONSTRUCTION, SCORPION ALPHA-TOXINS, VENOM PEPTIDES, CYSTINE-KNOT, CALCIUM-CHANNELS, NMR-SPECTROSCOPY, SNOWDROP LECTIN, DISULFIDE BONDS, CA2+ CURRENTS

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MLA
Bende, Niraj S, Slawomir Dziemborowicz, Volker Herzig, et al. “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 (2015): 904–920. Print.
APA
Bende, N. S., Dziemborowicz, S., Herzig, V., Ramanujam, V., Brown, G. W., Bosmans, F., Nicholson, G. M., et al. (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.
Chicago author-date
Bende, Niraj S, Slawomir Dziemborowicz, Volker Herzig, Venkatraman Ramanujam, Geoffrey W Brown, Frank Bosmans, Graham M Nicholson, Glenn F King, and Mehdi Mobli. 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.
Chicago author-date (all authors)
Bende, Niraj S, Slawomir Dziemborowicz, Volker Herzig, Venkatraman Ramanujam, Geoffrey W Brown, Frank Bosmans, Graham M Nicholson, Glenn F King, and Mehdi Mobli. 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.
Vancouver
1.
Bende NS, Dziemborowicz S, Herzig V, Ramanujam V, Brown GW, Bosmans F, et al. 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. 2015;282(5):904–20.
IEEE
[1]
N. S. Bende et al., “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, vol. 282, no. 5, pp. 904–920, 2015.
@article{8584519,
  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 beta-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.},
  author       = {Bende, Niraj S and Dziemborowicz, Slawomir and Herzig, Volker and Ramanujam, Venkatraman and Brown, Geoffrey W and Bosmans, Frank and Nicholson, Graham M and King, Glenn F and Mobli, Mehdi},
  issn         = {1742-464X},
  journal      = {FEBS JOURNAL},
  keywords     = {disulfide-rich peptide,heteronuclear NMR,pore blocker,spider toxin,voltage-gated sodium channel,FUNNEL-WEB SPIDERS,MAXIMUM-ENTROPY RECONSTRUCTION,SCORPION ALPHA-TOXINS,VENOM PEPTIDES,CYSTINE-KNOT,CALCIUM-CHANNELS,NMR-SPECTROSCOPY,SNOWDROP LECTIN,DISULFIDE BONDS,CA2+ CURRENTS},
  language     = {eng},
  number       = {5},
  pages        = {904--920},
  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},
  url          = {http://dx.doi.org/10.1111/febs.13189},
  volume       = {282},
  year         = {2015},
}

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