A bimodal activation mechanism underlies scorpion toxin-induced pain

Shilong Yang, Fan Yang, Bei Zhang, Bo Hyun Lee, Bowen Li, Lei Luo, Jie Zheng, Ren Lai

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Venomous animals use peptide toxins for hunting and self-defense. To achieve these goals, toxins need to bind to their targets with high affinity due to the small amount that a single bite or sting can deliver. The scorpion toxin BmP01 is linked to sting-induced excruciating pain; however, the reported minimum concentrations for activating TRPV1 channel or inhibiting voltage-gated potassium (Kv) channels (both in the micromolar range) appear too high to be biologically relevant. We show that the effective concentration of BmP01 is highly pH-dependent-it increases by about 10-fold in inhibiting Kv channels upon a 1-U drop in pH but decreases more than 100-fold in activating TRPV1. Mechanistic investigation revealed that BmP01 binds to one of the two proton-binding sites on TRPV1 and, together with a proton, uses a one-two punch approach to strongly activate the nociceptive channel. Because most animal venoms are acidic, proton-facilitated synergistic action may represent a general strategy for maximizing toxin potency.

Original languageEnglish (US)
Article number1700810
JournalScience advances
Volume3
Issue number8
DOIs
StatePublished - Jan 1 2017

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Scorpions
Protons
Bites and Stings
Pain
Voltage-Gated Potassium Channels
Venoms
Binding Sites
Peptides

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yang, S., Yang, F., Zhang, B., Lee, B. H., Li, B., Luo, L., ... Lai, R. (2017). A bimodal activation mechanism underlies scorpion toxin-induced pain. Science advances, 3(8), [1700810]. https://doi.org/10.1126/sciadv.1700810

A bimodal activation mechanism underlies scorpion toxin-induced pain. / Yang, Shilong; Yang, Fan; Zhang, Bei; Lee, Bo Hyun; Li, Bowen; Luo, Lei; Zheng, Jie; Lai, Ren.

In: Science advances, Vol. 3, No. 8, 1700810, 01.01.2017.

Research output: Contribution to journalArticle

Yang, S, Yang, F, Zhang, B, Lee, BH, Li, B, Luo, L, Zheng, J & Lai, R 2017, 'A bimodal activation mechanism underlies scorpion toxin-induced pain', Science advances, vol. 3, no. 8, 1700810. https://doi.org/10.1126/sciadv.1700810
Yang S, Yang F, Zhang B, Lee BH, Li B, Luo L et al. A bimodal activation mechanism underlies scorpion toxin-induced pain. Science advances. 2017 Jan 1;3(8). 1700810. https://doi.org/10.1126/sciadv.1700810
Yang, Shilong ; Yang, Fan ; Zhang, Bei ; Lee, Bo Hyun ; Li, Bowen ; Luo, Lei ; Zheng, Jie ; Lai, Ren. / A bimodal activation mechanism underlies scorpion toxin-induced pain. In: Science advances. 2017 ; Vol. 3, No. 8.
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