The Tarantula Venom Peptide Eo1a Binds to the Domain II S3-S4 Extracellular Loop of Voltage-Gated Sodium Channel NaV1.8 to Enhance Activation

Jennifer R. Deuis; Lotten Ragnarsson; Samuel D. Robinson; Zoltan Dekan; Lerena Chan; Ai-Hua Jin; Poanna Tran; Kirsten L. McMahon; Shengnan Li; John N. Wood; James J. Cox; Glenn F. King; Volker Herzig; Irina Vetter

doi:10.3389/fphar.2021.789570

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The Tarantula Venom Peptide Eo1a Binds to the Domain II S3-S4 Extracellular Loop of Voltage-Gated Sodium Channel NaV1.8 to Enhance Activation

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The Tarantula Venom Peptide Eo1a Binds to the Domain II S3-S4 Extracellular Loop of Voltage-Gated Sodium Channel NaV1.8 to Enhance Activation

Jennifer R. Deuis, Lotten Ragnarsson, Samuel D. Robinson, Zoltan Dekan, Lerena Chan, Ai-Hua Jin, Poanna Tran, Kirsten L. McMahon, Shengnan Li, John N. Wood, …

Frontiers in Pharmacology, Vol.12, pp.1-10

2022

DOI: https://doi.org/10.3389/fphar.2021.789570

PMCID: PMC8795738

PMID: 35095499

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Abstract

Pain

Nav1.8

peptide

spider

voltage-gated sodium channel

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.

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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 Queensland
Lotten Ragnarsson (Author) - Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
Samuel D. Robinson (Author) - The University of Queensland
Zoltan Dekan (Author) - The University of Queensland
Lerena Chan (Author) - The University of Queensland
Ai-Hua Jin (Author) - Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
Poanna Tran (Author) - Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
Kirsten L. McMahon (Author) - The University of Queensland
Shengnan Li (Author) - Wolfson Institute for Biomedical Research, University College London, London, United Kingdom
John N. Wood (Author) - University College London
James J. Cox (Author) - Wolfson Institute for Biomedical Research, University College London, London, United Kingdom
Glenn F. King (Author) - The University of Queensland
Volker Herzig (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
Irina 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
PMID: 35095499; PMC8795738
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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