FEATURES

FAMILY

DESCRIPTION

Also known as TXH4_CYRSC, TXH4. This lethal neurotoxin (without cyclization at position 53) inhibits neuronal voltage-gated sodium channel Nav1.2/SCN2A (IC(50)=10-150 nM), rNav1.3/SCN3A (IC(50)=338 nM), Nav1.6/SCN8A (IC(50)=117 nM), and hNav1.7/SCN9A (IC(50)=9.6-33 nM) (PubMed:18628201, PubMed:20855463, PubMed:25658507, PubMed:29703751, PubMed:31234412, PubMed:23760503). It inhibits activation of sodium channel by trapping the voltage sensor of domain II (DIIS4) in the closed configuration (PubMed:18628201, PubMed:23760503). The toxin neither shifts the Nav1.7/SCN9A activation curve nor modifies the slope factor (PubMed:20855463). It does not slow fast-inactivation of hNav1.7/SCN9A channels (PubMed:20855463). In addition, it has only a weak affinity for lipid membranes (PubMed:18054060, PubMed:29703751, PubMed:28115115). This toxin also exists with a pyroglutamate at position 53 (PubMed:23826086). The sole difference observed between modified (mHwTx-IV) and unmodified toxins is that moderate or high depolarization voltages (200 mV) permit the unmodified toxin to dissociate, whereas mHwTx-IV toxin does not dissociate, even at high depolarization voltages (PubMed:23826086). These data indicate that mHwTx-IV strongly binds to voltage sensor of sodium channel even at extreme depolarization voltages (PubMed:23826086).

EXTERNAL LINKS

TXH4

Huwentoxin-IV

TXH4

Molecular Synopsis