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

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 sulfo...