2WFU

Crystal structure of DILP5 variant DB

Summary for 2WFU

• Entry DOI: 10.2210/pdb2wfu/pdb
• Related: 2WFV
• Descriptor: PROBABLE INSULIN-LIKE PEPTIDE 5 A CHAIN, PROBABLE INSULIN-LIKE PEPTIDE 5 B CHAIN (3 entities in total)
• Functional Keywords: cleavage on pair of basic residues, signaling protein
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY); More
• Cellular location: Secreted (Potential): Q7KUD5 Q7KUD5
• Total number of polymer chains: 2
• Total formula weight: 4915.62

Authors

Kulahin, N.,Schluckebier, G.,Sajid, W.,De Meyts, P. (deposition date: 2009-04-15, release date: 2010-05-26, Last modification date: 2024-10-23)

Primary citation

Sajid, W.,Kulahin, N.,Schluckebier, G.,Ribel, U.,Henderson, H.R.,Tatar, M.,Hansen, B.F.,Svendsen, A.M.,Kiselyov, V.V.,Norgaard, P.,Wahlund, P.,Brandt, J.,Kohanski, R.A.,Andersen, A.S.,De Meyts, P.
Structural and Biological Properties of the Drosophila Insulin-Like Peptide 5 Show Evolutionary Conservation.
J.Biol.Chem., 286:661-, 2011

PubMed Abstract: 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.

PubMed: 20974844
DOI: 10.1074/JBC.M110.156018

Experimental method

X-RAY DIFFRACTION (1.85 Å)