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

15 Scopus citations

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

ASJC Scopus subject areas

  • Medicine(all)

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