Scorpion toxin inhibits the voltage-gated proton channel using a Zn²⁺ -like long-range conformational coupling mechanism.

ABSTRACT:

Background and purpose

Blocking the voltage-gated proton channel H_V 1 is a promising strategy for the treatment of diseases like ischaemia stroke and cancer. However, few H_V 1 channel antagonists have been reported. Here, we have identified a novel H_V 1 channel antagonist from scorpion venom and have elucidated its action mechanism.

Experimental approach

H_V 1 and NaV channels were heterologously expressed in mammalian cell lines and their currents recorded using whole-cell patch clamp. Site-directed mutagenesis was used to generate mutants. Toxins were recombinantly produced in Escherichia coli. AGAP/W38F-H_V 1 interaction was modelled by molecular dynamics simulations.

Key results

The scorpion toxin AGAP (anti-tum

SUBMITTER: Tang D 

PROVIDER: S-EPMC7174885 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature