Milburn M V, Hassell A M, Lambert M H, Jordan S R, Proudfoot A E, Graber P, Wells T N
Laboratory of Molecular Medicine, Children's Hospital/Ender 673, Boston, Massachusetts 02115-5737.
Nature. 1993 May 13;363(6425):172-6. doi: 10.1038/363172a0.
Interleukin-5 (IL-5) is a lineage-specific cytokine for eosinophilpoiesis and plays an important part in diseases associated with increased eosinophils, such as asthma. Human IL-5 is a disulphide-linked homodimer with 115 amino-acid residues in each chain. The crystal structure at 2.4 A resolution reveals a novel two-domain structure, with each domain showing a striking similarity to the cytokine fold found in granulocyte macrophage and macrophage colony-stimulating factors, IL-2 (ref. 5), IL-4 (ref. 6), and human and porcine growth hormones. IL-5 is unique in that each domain requires the participation of two chains. The IL-5 structure consists of two left-handed bundles of four helices laid end to end and two short beta-sheets on opposite sides of the molecule. Surprisingly, the C-terminal strand and helix of one chain complete a bundle of four helices and a beta-sheet with the N-terminal three helices and one strand of the other chain. The structure of IL-5 provides a molecular basis for the design of antagonists and agonists that would delineate receptor recognition determinants critical in signal transduction. This structure determination extends the family of the cytokine bundle of four helices and emphasizes its fundamental significance and versatility in recognizing its receptor.
白细胞介素-5（IL-5）是嗜酸性粒细胞生成的谱系特异性细胞因子，在与嗜酸性粒细胞增多相关的疾病（如哮喘）中起重要作用。人IL-5是一种二硫键连接的同二聚体，每条链有115个氨基酸残基。分辨率为2.4埃的晶体结构揭示了一种新颖的双结构域结构，每个结构域与粒细胞巨噬细胞和巨噬细胞集落刺激因子、IL-2（参考文献5）、IL-4（参考文献6）以及人和猪生长激素中的细胞因子折叠有显著相似性。IL-5的独特之处在于每个结构域需要两条链的参与。IL-5结构由两个首尾相连的左旋四螺旋束和分子相对两侧的两个短β-折叠组成。令人惊讶的是，一条链的C末端链和螺旋与另一条链的N末端三个螺旋和一条链完成了一个四螺旋束和一个β-折叠。IL-5的结构为设计拮抗剂和激动剂提供了分子基础，这些拮抗剂和激动剂将描绘出信号转导中关键的受体识别决定因素。这种结构测定扩展了四螺旋细胞因子束家族，并强调了其在识别受体方面的基本重要性和多功能性。
