Tags

Type your tag names separated by a space and hit enter

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 J. 2015 Mar; 282(5):904-20.FJ

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.

Authors+Show Affiliations

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Qld, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25559770

Citation

Bende, Niraj S., 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." The FEBS Journal, vol. 282, no. 5, 2015, pp. 904-20.
Bende NS, Dziemborowicz S, Herzig V, 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 J. 2015;282(5):904-20.
Bende, N. S., Dziemborowicz, S., Herzig, V., Ramanujam, V., Brown, G. W., Bosmans, F., Nicholson, G. M., King, G. F., & Mobli, M. (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. The FEBS Journal, 282(5), 904-20. https://doi.org/10.1111/febs.13189
Bende NS, 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 J. 2015;282(5):904-20. PubMed PMID: 25559770.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Bende,Niraj S, AU - Dziemborowicz,Sławomir, AU - Herzig,Volker, AU - Ramanujam,Venkatraman, AU - Brown,Geoffrey W, AU - Bosmans,Frank, AU - Nicholson,Graham M, AU - King,Glenn F, AU - Mobli,Mehdi, Y1 - 2015/01/23/ PY - 2014/06/10/received PY - 2014/12/15/revised PY - 2014/12/27/accepted PY - 2015/1/7/entrez PY - 2015/1/7/pubmed PY - 2015/5/6/medline KW - disulfide-rich peptide KW - heteronuclear NMR KW - pore blocker KW - spider toxin KW - voltage-gated sodium channel SP - 904 EP - 20 JF - The FEBS journal JO - FEBS J VL - 282 IS - 5 N2 - 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. SN - 1742-4658 UR - https://www.unboundmedicine.com/medline/citation/25559770/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_ L2 - https://doi.org/10.1111/febs.13189 DB - PRIME DP - Unbound Medicine ER -