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

@article{Milburn1993AND,
  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},
  journal={Nature},
  year={1993},
  volume={363},
  pages={172-176}
}
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
TLDR
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
TLDR
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
TLDR
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*
TLDR
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*
TLDR
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.
TLDR
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 (*)
TLDR
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
TLDR
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.
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