Addition of K22 converts spider venom peptide Pme2a from an activator to an inhibitor of NaV1.7

Kathleen Yin, Jennifer R. Deuis, Zoltan Dekan, Ai-Hua Jin, Paul F. Alewood, Glenn F. King, Volker Herzig*, Irina Vetter

*Corresponding author for this work

Research output: Contribution to journalArticle

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Spider venom is a novel source of disulfide-rich peptides with potent and selective activity at voltage-gated sodium channels (NaV). Here, we describe the discovery of μ-theraphotoxin-Pme1a and μ/δ-theraphotoxin-Pme2a, two novel peptides from the venom of the Gooty Ornamental tarantula Poecilotheria metallica that modulate NaV channels. Pme1a is a 35 residue peptide that inhibits NaV1.7 peak current (IC50 334 ± 114 nM) and shifts the voltage dependence of activation to more depolarised membrane potentials (V1/2 activation: Δ =+11.6 mV). Pme2a is a 33 residue peptide that delays fast inactivation and inhibits NaV1.7 peak current (EC50 > 10 μM). Synthesis of a [+22K]Pme2a analogue increased potency at NaV1.7 (IC50 5.6 ± 1.1 μM) and removed the effect of the native peptide on fast inactivation, indicating that a lysine at position 22 (Pme2a numbering) is important for inhibitory activity. Results from this study may be used to guide the rational design of spider venom-derived peptides with improved potency and selectivity at NaV channels in the future.

Original languageEnglish
Article number37
Pages (from-to)1-9
Number of pages9
Issue number2
Publication statusPublished - 19 Feb 2020

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Na1.7
  • Na1.8
  • Peptide
  • Sodium channel
  • Spider
  • Venom

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