PubMed 26420335

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPV , TRPV1

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

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

Journal, date & volume: Nat Commun, 2015 , 6, 8297

PubMed link:

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.