8.B.5.3.8
K⁺ channel blocker, a gating modifier toxin that inhibits by binding to the voltage sensor domain (VSD) of various VIC superfamily members, VSTx1 of 62 aas and 1 TMS (Ozawa et al. 2015). Many spider-venom peptides function as gating modifiers by binding to the VSDs of voltage-gated channels and trapping them in a closed or open state (Lau et al. 2016). The toxin interacts with residues in an aqueous cleft formed between the extracellular S1-S2 and S3-S4 loops of the VSD whilst maintaining lipid interactions in the gaps formed between the S1-S4 and S2-S3 helices. The resulting network of interactions increases the energetic barrier to the conformational changes required for channel gating, and this is the mechanism by which gating modifier toxins inhibit voltage-gated ion channels (Lau et al. 2016).