Toxicon 2013 Mar 01;63:129-36. doi: 10.1016/j.toxicon.2012.12.001.

Molecular determinants for the tarantula toxin jingzhaotoxin-I interacting with potassium channel Kv2.1.

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With high binding affinity and distinct pharmacological functions, animal toxins are powerful ligands to investigate the structure-function relationships of voltage-gated ion channels. Jingzhaotoxin-I (JZTX-I) is an important neurotoxin from the tarantula Chilobrachys jingzhao venom that inhibits both sodium and potassium channels. In our previous work, JZTX-I, as a gating modifier, is able to inhibit activation of the potassium channel subtype Kv2.1. However, its binding site on Kv2.1 remains unknown. In this study, using Ala-scanning mutagenesis strategy, we demonstrated that four residues (I273, F274, E277, and K280) in S3b-S4 motif contributed to the formation of JZTX-I binding site. The mutations I273A, F274A, E277A, and K280A reduced toxin binding affinity by 6-, 10-, 8-, and 7-fold, respectively. Taken together with our previous data that JZTX-I accelerated channel deactivation, these results suggest that JZTX-I inhibits Kv2.1 activation by docking onto the voltage sensor paddle and trapping the voltage sensor in the closed state.

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Species referenced: Xenopus laevis
Genes referenced: kcnb1