2WFU

Crystal structure of DILP5 variant DB

2WFU の概要

• エントリーDOI: 10.2210/pdb2wfu/pdb
• 関連するPDBエントリー: 2WFV
• 分子名称: PROBABLE INSULIN-LIKE PEPTIDE 5 A CHAIN, PROBABLE INSULIN-LIKE PEPTIDE 5 B CHAIN (3 entities in total)
• 機能のキーワード: cleavage on pair of basic residues, signaling protein
• 由来する生物種: DROSOPHILA MELANOGASTER (FRUIT FLY); 詳細
• 細胞内の位置: Secreted (Potential): Q7KUD5 Q7KUD5
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 4915.62

構造登録者

Kulahin, N.,Schluckebier, G.,Sajid, W.,De Meyts, P. (登録日: 2009-04-15, 公開日: 2010-05-26, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.85 Å)