ProTx-II acts as an antagonist of Nav1.7 by binding to the voltage-sensor domain 2 (VSD-II) of the channel. The toxin inhibits the activation of Nav channels by binding to the linker in the L3-4 loop (between the S3 and S4 segments) above the central cavity of VSD-II, which is known as site 4. ProTx-II inhibits sodium currents by shifting the voltage-dependence of the channel activation to more positive potentials. The toxin uses a similar action mechanism on the Cav1.2 and Cav1.3 voltage-gated calcium channels: shifting the activation of these L-type and T-type calcium channels, respectively, to more positive voltages. ProTx-II also inhibits fast inactivation of the Nav channel by binding to VSD-IV in the resting configuration of the channel. The inhibition of activation and of inactivation appear to be independent processes. For instance, mutations in domain IV substantially affect the inhibition of inactivation without changing the inhibition of activation by ProTx-II. Likewise, mutations in domain<unk>  mostly affect the inhibition of activation. Therefore, it seems that ProTx-II is able to interact with two independent sites (DIV and DII) at the same time. Another factor that supports this theory is the estimated IC50. The IC50 for inhibition of activation is approximately 400-fold smaller than the one calculated for inhibition of inactivation, again suggesting that the inhibition of activation and the inhibition of inactivation are independent processes.
Protoxin-II
Alpha-neurotoxin
Kaliotoxin
Delta-Palutoxin
Kurtoxin
Maitotoxin
Β-Bungarotoxin
Conotoxin