A novel dimer configuration revealed by the crystal structure at 2.4 Å resolution of human interleukin-5

  title={A novel dimer configuration revealed by the crystal structure at 2.4 Å resolution of human interleukin-5},
  author={Michael Vance Milburn and Anne M. Hassell and Millard H. Lambert and Steven R. Jordan and Amanda E. I. Proudfoot and Pierre Graber and Timothy Nigel Carl Wells},
INTERLEUKIN-5 (IL-5) is a lineage-specific cytokine for eosinophilpoiesis and plays an important part in diseases associ-ated with increased eosinophils, such as asthma1,2. Human IL-5 is a disulphide-linked homodimer with 115 amino-acid residues in each chain2. The crystal structure at 2.4 Å resolution reveals a novel two-domain structure, with each domain showing a striking similarity to the cytokine fold found in granulocyte macrophage3 and macrophage4 colony-stimulating factors, IL-2 (ref. 5… 
The Three‐Dimensional Structure of Human Interleukin‐5 at 2.4‐Angstroms Resolution: Implication for the Structures of Other Cytokines
The three-dimensional structure of human 1L-5 is solved to a resolution of 2.4 A using X-ray crystallographic techniques and reveals a novel two-domain structure where each domain of the protein is a 4-helical bundle containing two short stretches of beta sheet.
Engineering of a functional interleukin-5 monomer: a paradigm for redesigning helical bundle cytokines with therapeutic potential in allergy and asthma
No differences in signal transduction pathways utilized by mono5 and IL-5 are demonstrated, as determined by western blot analysis of early tyrosine phosphorylation events, Jak2 activation, and mitogen-activated protein kinase activation.
Creation of a biologically active interleukin-5 monomer
These studies demonstrate that all of the structural features necessary for IL-5 to function are contained within a single helical bundle.
Spatial Orientation of the α and βc Receptor Chain Binding Sites on Monomeric Human Interleukin-5 Constructs*
Results indicate that activation of the IL-5 receptor complex is not mediated solely by Glu12 on the first helix, and alternative mechanisms are discussed.
Design and Analysis of an Engineered Human Interleukin-10 Monomer*
Results indicate that the 1:1 interaction between IL-10M1 and IL-11Rβ is sufficient for recruiting the signal transducing receptor chain (IL-10Rβ) into the signaling complex and eliciting IL- 10 cellular responses.
Structural and evolutionary exploration of the IL-3 family and its alpha subunit receptors.
It is highlighted that IL-3 andIL-3Rα structural architectures are conserved across evolution and shared with other proteins belonging to the same βc family interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF).
Identification of Key Charged Residues of Human Interleukin-5 in Receptor Binding and Cellular Activation (*)
The α-chain binding site is shown to involve the side chains Arg-90 and Glu-109, located in the second β sheet and after the end of the fourth helix, respectively, which is unique to IL-5 and does not occur in IL-3 or GM-CSF.
The carboxy-terminal region of human interleukin-5 is essential for maintenance of tertiary structure but not for dimerization
The C-terminal region of interleukin-5 has previously been suggested to be important for biological activity and is investigated by making a series of truncation mutants, which showed a rapid loss of activity and a drop in binding affinity to both theα chain of the receptor and the high-affinity complex consisting of theα andβ subunits.


Structural design and molecular evolution of a cytokine receptor superfamily.
  • J. Bazan
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1990
This work proposes that the approximately 200-residue binding segment of the canonical cytokine receptor is composed of two discrete folding domains that share a significant sequence and structural resemblance with a likely binding site for cytokine ligands.
Three-dimensional structure of dimeric human recombinant macrophage colony-stimulating factor.
Individual monomers of M-CSF show a close structural similarity to the cytokines granulocyte-macrophage colony-stimulating factor and human growth hormone, which suggests that the receptor binding determinants for all three cytokines may be similar.
Three-dimensional structure of interleukin 8 in solution.
It is suggested that the two alpha-helices form the binding site for the cellular receptor and that the specificity of IL-8, as well as that of a number of related proteins involved in cell-specific chemotaxis, mediation of cell growth, and the inflammatory response, is achieved by the distinct distribution of charged and polar residues at the surface of the helices.
Conformational homologies among cytokines: Interleukins and colony stimulating factors
Structures are suggested for huG‐CSF, huGM‐ CSF and muIL‐5 in which defined loop segments at the ends of helical bundles are the most likely sites for binding and recognition by specific cell receptors.
Human growth hormone and extracellular domain of its receptor: crystal structure of the complex.
Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor.
Structure‐function analysis of interleukin‐5 utilizing mouse/human chimeric molecules.
In the mouse cell assays, the hybrids clearly identified the importance of residues in the C terminus for biological activity, and competition binding assays showed that this region probably interacts with the receptor.
Structure of recombinant human interleukin 5 produced by Chinese hamster ovary cells.
The complete peptide map of purified recombinant human interleukin 5 was determined to verify its primary structure, glycosylation sites, and disulfide bonding structure and indicate that primary structure of rhIL-5 is highly homogeneous and observed heterogeneity is due to the difference in the content of carbohydrate.
Crystallization and preliminary X-ray diffraction studies of recombinant human interleukin-5.
Recombinant human interleukin-5 (rhIL-5) has been crystallized by the hanging drop vapor diffusion method using 0.1 M-Tris and the molecular mass weight and volume suggest that the asymmetric unit contains one intermolecular disulfide-bonded homodimer.