Solution structure of Jingzhaotoxin-III, a peptide toxin inhibiting both Nav1.5 and Kv2.1 channels.

Jingzhaotoxin-III (JZTX-III) is a peptide toxin isolated from the venom of the Chinese spider Chilobrachys jingzhao that inhibits Nav channels of rat cardiac myocytes by modifying voltage-dependent gating and also binds to Kv2.1 channel (Kd = 0.43 microM) with an action model similar to that of hanatoxin1 and SGTx1. The solution structure of JZTX-III was determined by (1)H 2D NMR method. The toxin adopts an ICK motif composed of three beta-strands connected by four turns. Structural comparison of JZTX-III with those of other ICK motif peptides shows that they all adopt a conserved surface profile, a hydrophobic patch surrounded by charged residues, which might be the crucial site for voltage-gating ion channel inhibition. Furthermore, the similar action model of JZTX-III affecting both Kv and Nav channels implies that JZTX-III recognized a conserved receptor within the voltage sensing domains, which is similar to that of hanatoxin1 binding to both Kv and Cav channels.