Structural Basis for High-Affinity Trapping of the Na_V1.7 Channel in Its Resting State by Tarantula Toxin.

ABSTRACT: Voltage-gated sodium channels initiate electrical signals and are frequently targeted by deadly gating-modifier neurotoxins, including tarantula toxins, which trap the voltage sensor in its resting state. The structural basis for tarantula-toxin action remains elusive because of the difficulty of capturing the functionally relevant form of the toxin-channel complex. Here, we engineered the model sodium channel Na_VAb with voltage-shifting mutations and the toxin-binding site of human Na_V1.7, an attractive pain target. This mutant chimera enabled us to determine the cryoelectron microscopy (cryo-EM) structure of the channel functionally arrested by tarantula toxin. Our structure reveals a high-affinity resting-state-specific toxin-channel interaction between a key lysin

SUBMITTER: Wisedchaisri G 

PROVIDER: S-EPMC8043720 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature