8.b.41. The Centipede Toxin (RhTx) Family
Au-scoloptoxin(04)-Sm1b of 69 aas and 1 TMS is an extremely potent potentiator of TRPV1 (EC(50)=521.5 nM) that strongly promotes the heat activation process by downshifting the activation threshold temperature. It preferably binds to the activated channel and promotes its opening. Holding the channel closed by cooling prevents binding of this toxin, leaving it ineffective. The toxin binds to the charge-rich outer pore region of the channel where it directly interacts with the pore helix and turret, two adjacent structural elements known to be critical for activation gating of TRPV1. In vivo, it induces pain in mice after intraplantar injection (Yang et al. 2015).