The modes of action of ion-channel-targeting neurotoxic insecticides: lessons from structural biology. 

Raisch T, Raunser S.  Nat Struct Mol Biol. (2023)

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Insecticides are indispensable tools for plant protection in modern agriculture. Despite having highly heterogeneous structures, many neurotoxic insecticides use similar principles to inhibit or deregulate neuronal ion channels. Insecticides targeting pentameric ligand-gated channels are structural mimetics of neurotransmitters or manipulate and deregulate the proteins. Those binding to (pseudo-)tetrameric voltage-gated(-like) channels, on the other hand, are natural or synthetic compounds that directly block the ion-conducting pore or prevent conformational changes in the transmembrane domain necessary for opening and closing the pore. The use of a limited number of inhibition mechanisms can be problematic when resistances arise and become more widespread. Therefore, there is a rising interest in the development of insecticides with novel mechanisms that evade resistance and are pest-insect-specific. During the last decade, most known insecticide targets, many with bound compounds, have been structurally characterized, bringing the rational design of novel classes of agrochemicals within closer reach than ever before.