A NOVEL DIMER CONFIGURATION REVEALED BY THE CRYSTAL-STRUCTURE AT 2.4 ANGSTROM RESOLUTION OF HUMAN INTERLEUKIN-5

INTERLEUKIN-5 (IL-5) is a lineage-specific cytokine for eosinophilpoie sis and plays an important part in diseases associated with increased eosinophils, such as asthma1,2. Human IL-5 is a disulphide-linked homo dimer with 115 amino-acid residues in each chain 2. The crystal struct ure at 2.4 angstrom resolution reveals a novel two-domain structure, w ith each domain showing a striking similarity to the cytokine fold fou nd in granulocyte macrophage3 and macrophage4 colony-stimulating facto rs, IL-2 (ref. 5), IL-4 (ref. 6), and human7 and porcine8 growth hormo nes. 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 sid es of the molecule. Surprisingly, the C-terminal strand and helix of o ne 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 structu re of IL-5 provides a molecular basis for the design of antagonists an d agonists that would delineate receptor recognition determinants crit ical in signal transduction. This structure determination extends the family of the cytokine bundle of four helices and emphasizes its funda mental significance and versatility in recognizing its receptor.