Structural highlights
Function
H3A01_CYRHA Selective antagonist of neuronal tetrodotoxin (TTX)-sensitive voltage-gated sodium channels (IC(50)=1270 nM on Nav1.1/SCN1A, 270 nM on Nav1.2/SCN2A, 491 nM on Nav1.3/SCN3A and 232 nM on Nav1.7/SCN9A). This toxin suppress Nav1.7 current amplitude without significantly altering the activation, inactivation, and repriming kinetics. Short extreme depolarizations partially activate the toxin-bound channel, indicating voltage-dependent inhibition of this toxin. This toxin increases the deactivation of the Nav1.7 current after extreme depolarizations. The toxin-Nav1.7 complex is gradually dissociated upon prolonged strong depolarizations in a voltage-dependent manner, and the unbound toxin rebinds to Nav1.7 after a long repolarization. Moreover, analysis of chimeric channels showed that the DIIS3-S4 linker is critical for toxin binding to Nav1.7. These data are consistent with this toxin interacting with Nav1.7 site 4 and trapping the domain II voltage sensor in the closed state.[1]
References
- ↑ Liu Z, Cai T, Zhu Q, Deng M, Li J, Zhou X, Zhang F, Li D, Li J, Liu Y, Hu W, Liang S. Structure and function of hainantoxin-III, a selective antagonist of neuronal tetrodotoxin-sensitive voltage-gated sodium channels isolated from the Chinese bird spider Ornithoctonus hainana. J Biol Chem. 2013 Jul 12;288(28):20392-403. PMID:23703613 doi:10.1074/jbc.M112.426627
