A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1

Shilong Yang, Fan Yang, Ningning Wei, Jing Hong, Bowen Li, Lei Luo, Mingqiang Rong, Vladimir Yarov-Yarovoy, Jie Zheng, Kewei Wang, Ren Lai

Research output: Contribution to journalArticle

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Abstract

The capsaicin receptor TRPV1 ion channel is a polymodal nociceptor that responds to heat with exquisite sensitivity through an unknown mechanism. Here we report the identification of a novel toxin, RhTx, from the venom of the Chinese red-headed centipede that potently activates TRPV1 to produce excruciating pain. RhTx is a 27-amino-acid small peptide that forms a compact polarized molecule with very rapid binding kinetics and high affinity for TRPV1. We show that RhTx targets the channel's heat activation machinery to cause powerful heat activation at body temperature. The RhTx-TRPV1 interaction is mediated by the toxin's highly charged C terminus, which associates tightly to the charge-rich outer pore region of the channel where it can directly interact with the pore helix and turret. These findings demonstrate that RhTx binding to the outer pore can induce TRPV1 heat activation, therefore providing crucial new structural information on the heat activation machinery.

Original languageEnglish (US)
Article number8297
JournalNature Communications
Volume6
DOIs
StatePublished - Sep 30 2015

Fingerprint

Nociceptors
pain
machinery
Machinery
Hot Temperature
Chemical activation
activation
Pain
heat
porosity
turret
body temperature
TRPV Cation Channels
Venoms
Body Temperature
Ion Channels
helices
peptides
amino acids
affinity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1. / Yang, Shilong; Yang, Fan; Wei, Ningning; Hong, Jing; Li, Bowen; Luo, Lei; Rong, Mingqiang; Yarov-Yarovoy, Vladimir; Zheng, Jie; Wang, Kewei; Lai, Ren.

In: Nature Communications, Vol. 6, 8297, 30.09.2015.

Research output: Contribution to journalArticle

Yang, Shilong ; Yang, Fan ; Wei, Ningning ; Hong, Jing ; Li, Bowen ; Luo, Lei ; Rong, Mingqiang ; Yarov-Yarovoy, Vladimir ; Zheng, Jie ; Wang, Kewei ; Lai, Ren. / A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1. In: Nature Communications. 2015 ; Vol. 6.
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