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The Tarantula Venom Peptide Eo1a Binds to teh Domain II S3-S4 Extracellular Loop of VOltage-Gated Sodium Channel Nav1.8 to Enhance Activation2.29 MB
Published VersionCC BY V4.0, Open Access
Journal article
The Tarantula Venom Peptide Eo1a Binds to the Domain II S3-S4 Extracellular Loop of Voltage-Gated Sodium Channel NaV1.8 to Enhance Activation
Frontiers in Pharmacology, Vol.12, pp.1-10
2022
Abstract
Venoms from cone snails and arachnids are a rich source of peptide modulators of voltage-gated sodium (NaV) channels, however relatively few venom-derived peptides with activity at the mammalian NaV1.8 subtype have been isolated. Here, we describe the discovery and functional characterisation of β-theraphotoxin-Eo1a, a peptide from the venom of the Tanzanian black and olive baboon tarantula Encyocratella olivacea that modulates NaV1.8. Eo1a is a 37-residue peptide that increases NaV1.8 peak current (EC50 894 ± 146 nM) and causes a large hyperpolarising shift in both the voltage-dependence of activation (ΔV50–20.5 ± 1.2 mV) and steady-state fast inactivation (ΔV50–15.5 ± 1.8 mV). At a concentration of 10 μM, Eo1a has varying effects on the peak current and channel gating of NaV1.1–NaV1.7, although its activity is most pronounced at NaV1.8. Investigations into the binding site of Eo1a using NaV1.7/NaV1.8 chimeras revealed a critical contribution of the DII S3-S4 extracellular loop of NaV1.8 to toxin activity. Results from this work may form the basis for future studies that lead to the rational design of spider venom-derived peptides with improved potency and selectivity at NaV1.8.
Details
- Title
- The Tarantula Venom Peptide Eo1a Binds to the Domain II S3-S4 Extracellular Loop of Voltage-Gated Sodium Channel NaV1.8 to Enhance Activation
- Authors
- Jennifer R. Deuis (Author) - The University of QueenslandLotten Ragnarsson (Author) - Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, AustraliaSamuel D. Robinson (Author) - The University of QueenslandZoltan Dekan (Author) - The University of QueenslandLerena Chan (Author) - The University of QueenslandAi-Hua Jin (Author) - Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, AustraliaPoanna Tran (Author) - Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, AustraliaKirsten L. McMahon (Author) - The University of QueenslandShengnan Li (Author) - Wolfson Institute for Biomedical Research, University College London, London, United KingdomJohn N. Wood (Author) - University College LondonJames J. Cox (Author) - Wolfson Institute for Biomedical Research, University College London, London, United KingdomGlenn F. King (Author) - The University of QueenslandVolker Herzig (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyIrina Vetter (Corresponding Author) - The University of Queensland
- Publication details
- Frontiers in Pharmacology, Vol.12, pp.1-10
- Publisher
- Frontiers Research Foundation
- Date published
- 2022
- DOI
- 10.3389/fphar.2021.789570
- ISSN
- 1663-9812
- Copyright note
- Copyright © 2022 Deuis, Ragnarsson, Robinson, Dekan, Chan, Jin, Tran, McMahon, Li, Wood, Cox, King, Herzig and Vetter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Organisation Unit
- University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99608308902621
- Output Type
- Journal article
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