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Structural basis for the poisonous activity of a predator's venom insulin

A potent toxin present in the venom of a fish-hunting cone snail is a minimized insulin (Con-Ins G1) lacking key residues involved in the receptor binding of most insulins. New data show that Con-Ins G1 nevertheless binds potently to the human insulin receptor, owing to a rearrangement that compensates for the lack of a critical binding residue.

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Figure 1: Fish-hunting cone snails and their venom insulin.

Marina Corral Spence/Nature Publishing Group

Figure 2: Crystal structure of the complex between human insulin and insulin receptor site 1 (α-CT plus L1).
Figure 3: Canonical three-dimensional structure of insulin-like peptides.

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P.D.M. is an external consultant for Novo Nordisk A/S, Måløv, Denmark.

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De Meyts, P. Structural basis for the poisonous activity of a predator's venom insulin. Nat Struct Mol Biol 23, 872–874 (2016). https://doi.org/10.1038/nsmb.3304

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