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New mode of action for a knottin bioinsecticide: Pea Albumin 1 subunit b (PA1b) is the first peptidic inhibitor of V-ATPase.
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Edité par CCSD ; American Society for Biochemistry and Molecular Biology -
International audience. PA1b (for Pea Albumin 1 subunit b) is a plant bioinsecticide lethal for several pests which are important in agriculture or human health. PA1b belongs to the inhibitory cystine knot (ICK) family or knottin family. Originating from a plant (the garden pea) commonly eaten by humans without any known toxic or allergic effects, PA1b is a candidate for transgenic applications and is one of the most promising biopesticide for pest control. Using whole-cell patch clamp techniques on Sf9 PA1b-sensible Lepidopteran insect cells, we discover that PA1b reversibly blocks ramp membrane currents in a dose dependent manner (EC50 = 0.52 uM). PA1b has the same effect as bafilomycin, a specific inhibitor of the vacuolar proton pump (V-H+-ATPase), and the PA1b-sensitive current depends on the internal proton concentration. Biochemical assays on purified V-ATPase from the Lepidopteran model Manduca sexta showed that PA1b inhibits the V1V0-H+ ATPase holoenzyme activity (IC50 ca. 70 nM), by interacting with the membrane bound V0 part of the V-ATPase. V-ATPase is a complex protein which is increasingly studied because of its numerous physiological roles. In the midgut of insects, V-ATPase activity is essential for energizing nutrient absorption and the results reported in this paper explain the entomotoxic properties of PA1b. Targeting V-ATPase is a promising means of combating insect pests, and PA1b represents the first peptidic V-ATPase inhibitor. The search for V-ATPase inhibitors is currently booming, since it has been demonstrated that V-ATPase plays a role in so many physiological processes.
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