2mva

Structural highlights

Function

TX41A_SCOMU Extremely potent agonist and potentiator of TRPV1 (EC(50)=470-521.5 nM (mouse)) (PubMed:26420335, PubMed:32097697). It strongly promotes the heat activation process by downshifting the activation threshold temperature (PubMed:26420335). It preferably binds to the activated channel and promotes its opening (PubMed:26420335). Holding the channel closed by cooling prevents binding of this toxin, leaving it ineffective (PubMed:26420335). 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 (PubMed:26420335). In comparison with Sm1b, induces a TRPV1 desensitization with slower kinetics (20 seconds) (PubMed:32097697). In vivo, induces pain in mice after intraplantar injection (PubMed:26420335).^{[1] [2]} Potent agonist and probable potentiator of TRPV1 (EC(50)=38.35 uM (mouse)) (PubMed:32097697). Also binds to the outer pore region of TRPV1 (PubMed:32097697). In comparison with Sm1a, induces a TRPV1 desensitization with faster kinetics (2 seconds) and leads to a more complete TRPV1 desensitization (PubMed:32097697). Desensitization is achieved by reducing both the open probability and the single-channel conductance upon prolonged exposure (PubMed:32097697).^[3]

References

1. ↑ Yang S, Yang F, Wei N, Hong J, Li B, Luo L, Rong M, Yarov-Yarovoy V, Zheng J, Wang K, Lai R. A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1. Nat Commun. 2015 Sep 30;6:8297. PMID:26420335 doi:10.1038/ncomms9297
2. ↑ Zhu A, Aierken A, Yao Z, Vu S, Tian Y, Zheng J, Yang S, Yang F. A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel. Toxicon. 2020 Apr 30;178:41-49. PMID:32097697 doi:10.1016/j.toxicon.2020.02.016
3. ↑ Zhu A, Aierken A, Yao Z, Vu S, Tian Y, Zheng J, Yang S, Yang F. A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel. Toxicon. 2020 Apr 30;178:41-49. PMID:32097697 doi:10.1016/j.toxicon.2020.02.016