The Molecular Recognition Of The Insecticide Sulfoxaflor By Nicotinic Receptors Is Based On Atomic Interactions Identical To Bee‐Harming Neonicotinoids

Abstract

Neonicotinoids, sometimes called ‘neonics’, are a class of insecticides targeting neuronal nicotinic acetylcholine receptors, which belong to the family of pentameric ligand-gated ion channels (pLGICs) or Cys-loop receptors. The widespread application of these neurotoxic insecticides in agriculture is tied to the worldwide decline of bee populations, due to their sublethal effects on bee memory, behavior and reproduction. In 2018, the member states of the European Union, agreed on a ban of most neonicotinoids, with exemption for greenhouses. However, a new generation of sulfoximine-based insecticides, such as sulfoxaflor, has recently been introduced to the agricultural market claiming they are chemically distinct from neonicotinoids. Using the acetylcholine binding protein (AChBP) as a well-established tool for structural studies of nicotinic receptors, we engineered AChBP variants that reliably mimic the neurotransmitter binding site of honeybee nicotinic receptors. Three-dimensional structures of sulfoxaflor-bound receptors reveal, despite the distinct chemistry claim, that the molecule is recognized through receptor interactions that are virtually identical to neonicotinoids. This observation suggests that sulfoximine- and neonicotinoid-type insecticides share a common mode of action, and that the legislative ban on certain insecticides should, as a precaution, be expanded based on pharmacological activity at their target receptors rather than on chemical composition. Crystal structure of an insect nicotinic receptor mimic (iAChBP) in complex with the insecticide sulfoxaflor. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.