Structural and Biological Properties of the Drosophila Insulin-like Peptide 5 Show Evolutionary Conservation
Copyright policy )Structural and Biological Properties of the Drosophila Insulin-like Peptide 5 Show Evolutionary Conservation
We report the crystal structure of two variants of Drosophila melanogaster insulin-like peptide 5 (DILP5) at a resolution of 1.85 Å. DILP5 shares the basic fold of the insulin peptide family (T conformation) but with a disordered B-chain C terminus. DILP5 dimerizes in the crystal and in solution. The dimer interface is not similar to that observed in vertebrates, i.e. through an anti-parallel β-sheet involving the B-chain C termini but, in contrast, is formed through an anti-parallel β-sheet involving the B-chain N termini. DILP5 binds to and activates the human insulin receptor and lowers blood glucose in rats. It also lowers trehalose levels in Drosophila. Reciprocally, human insulin binds to the Drosophila insulin receptor and induces negative cooperativity as in the human receptor. DILP5 also binds to insect insulin-binding proteins. These results show high evolutionary conservation of the insulin receptor binding properties despite divergent insulin dimerization mechanisms.
- National Institutes of Health United States
- National Institute of Health Pakistan
- Brown University United States
- Novo Nordisk (Denmark) Denmark
Blood Glucose, Male, Models, Molecular, Protein Conformation, Lipogenesis, Molecular Sequence Data, Proteins, Crystallography, X-Ray, Rats, Evolution, Molecular, Iodine Radioisotopes, Mice, Drosophila melanogaster, Adipocytes, Animals, Humans, Insulin, Female, Amino Acid Sequence, Conserved Sequence
Blood Glucose, Male, Models, Molecular, Protein Conformation, Lipogenesis, Molecular Sequence Data, Proteins, Crystallography, X-Ray, Rats, Evolution, Molecular, Iodine Radioisotopes, Mice, Drosophila melanogaster, Adipocytes, Animals, Humans, Insulin, Female, Amino Acid Sequence, Conserved Sequence
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