ArticleThe Journal of biological chemistry2011
Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II and IV.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- The venom ofFrontiers in pharmacology · 2025Article
- Structure-function and rational design of a spider toxin Ssp1a at human voltage-gated sodium channel subtypes.Frontiers in pharmacology · 2023Article
- Structural Basis for High-Affinity Trapping of the NaMolecular cell · 2021Article
- Engineering of a Spider PeptideFrontiers in molecular biosciences · 2021Article
- Voltage-Gated Sodium Channel Modulation by a New Spider Toxin Ssp1a Isolated From an Australian Theraphosid.Frontiers in pharmacology · 2021Article
- Synthetic Analogues of Huwentoxin-IV Spider Peptide With Altered Human NaFrontiers in cell and developmental biology · 2021Article
- Pain-related toxins in scorpion and spider venoms: a face to face with ion channels.The journal of venomous animals and toxins including tropical diseases · 2021Review
- Employing NaChBac for cryo-EM analysis of toxin action on voltage-gated NaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Manipulation of a spider peptide toxin alters its affinity for lipid bilayers and potency and selectivity for voltage-gated sodium channel subtype 1.7.The Journal of biological chemistry · 2020Article
- Development of Photocrosslinking Probes Based on Huwentoxin-IV to Map the Site of Interaction on Nav1.7.Cell chemical biology · 2020Article
- Comprehensive engineering of the tarantula venom peptide huwentoxin-IV to inhibit the human voltage-gated sodium channel hNaThe Journal of biological chemistry · 2020Article
- Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways.Toxins · 2019Review
- Venom-Derived Peptide Modulators of Cation-Selective Channels: Friend, Foe or Frenemy.Frontiers in pharmacology · 2019Review
- Spider venom peptides as potential drug candidates due to their anticancer and antinociceptive activities.The journal of venomous animals and toxins including tropical diseases · 2019Review
- Spider toxin inhibits gating pore currents underlying periodic paralysis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7 : Differential activities of Nav1.7-targeting monoclonal antibodies.Neuroscience bulletin · 2018Article
- Insect-Active Toxins with Promiscuous Pharmacology from the African Theraphosid Spider Monocentropus balfouri.Toxins · 2017Article
- The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity.Scientific reports · 2017Article
- The structure, dynamics and selectivity profile of a NaV1.7 potency-optimised huwentoxin-IV variant.PloS one · 2017Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The voltage sensors of domains II and IV of sodium channels are important determinants of activation and inactivation, respectively. Animal toxins that alter electrophysiological excitability of muscles and neurons often modify sodium channel activation by selectively interacting with domain II and inactivation by selectively interacting with domain IV. This suggests that there may be substantial differences between the toxin-binding sites in these two important domains. Here we explore the ability of the tarantula huwentoxin-IV (HWTX-IV) to inhibit the activity of the domain II and IV voltage sensors. HWTX-IV is specific for domain II, and we identify five residues in the S1-S2 (Glu-753) and S3-S4 (Glu-811, Leu-814, Asp-816, and Glu-818) regions of domain II that are crucial for inhibition of activation by HWTX-IV. These data indicate that a single residue in the S3-S4 linker (Glu-818 in hNav1.7) is crucial for allowing HWTX-IV to interact with the other key residues and trap the voltage sensor in the closed configuration. Mutagenesis analysis indicates that the five corresponding residues in domain IV are all critical for endowing HWTX-IV with the ability to inhibit fast inactivation. Our data suggest that the toxin-binding motif in domain II is conserved in domain IV. Increasing our understanding of the molecular determinants of toxin interactions with voltage-gated sodium channels may permit development of enhanced isoform-specific voltage-gating modifiers.
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