果蝇胰岛素样肽 5 的结构和生物学特性表现出进化上的保守性。
Structural and biological properties of the Drosophila insulin-like peptide 5 show evolutionary conservation.
机构信息
Receptor Systems Biology Laboratory, Insulin and Incretin Biology, Hagedorn Research Institute, 2820 Gentofte, Denmark.
出版信息
J Biol Chem. 2011 Jan 7;286(1):661-73. doi: 10.1074/jbc.M110.156018. Epub 2010 Oct 25.
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.
摘要
我们报告了果蝇胰岛素样肽 5（DILP5）两种变体的晶体结构，分辨率为 1.85Å。DILP5 具有胰岛素肽家族的基本折叠（T 构象），但 B 链 C 末端无序。DILP5 在晶体中和溶液中均二聚化。二聚体界面与在脊椎动物中观察到的不同，即通过涉及 B 链 C 末端的反平行 β-片层，但相反，是通过涉及 B 链 N 末端的反平行 β-片层形成的。DILP5 结合并激活人胰岛素受体并降低大鼠的血糖。它还降低果蝇中的海藻糖水平。相反，人胰岛素与人胰岛素受体结合并诱导负协同作用，就像在人受体中一样。DILP5 也与昆虫胰岛素结合蛋白结合。这些结果表明，尽管胰岛素二聚化机制不同，但胰岛素受体结合特性具有高度的进化保守性。
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