IL-3, IL-5, and GM-CSF signaling: crystal structure of the human beta-common receptor.
The cytokines, interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage colony stimulating factor (GM-CSF), are polypeptide growth factors that exhibit overlapping activities in the regulation of hematopoietic cells. They appear to be primarily involved in inducible hematopoiesis in response to infections and are involved in the pathogenesis of allergic and inflammatory diseases and possibly in leukemia. The X-ray structure of the beta common (betac) receptor ectodomain has given new insights into the structural biology of signaling by IL-3, IL-5, and GM-CSF. This receptor is shared between the three ligands and functions together with three ligand-specific alpha-subunits. The structure shows betac is an intertwined homodimer in which each chain contains four domains with approximate fibronectin type-III topology. The two betac-subunits that compose the homodimer are interlocked by virtue of the swapping of beta-strands between domain 1 of one subunit and domain 3 of the other subunit. Site-directed mutagenesis has shown that the interface between domains 1 and 4 in this unique structure forms the functional epitope. This epitope is similar to those of other members of the cytokine class I receptor family but is novel in that it is formed by two different receptor chains. The chapter also reviews knowledge on the closely related mouse beta(IL-3) receptor and on the alpha-subunit-ligand interactions. The knowledge on the two beta receptors is placed in context with advances in understanding of the structural biology of other members of the cytokine class I receptor family.
Murphy
James M
JM
Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Acton, ACT, Australia 0200.
Young
Ian G
IG
D000818:Animals; D018360:Crystallography, X-Ray; D053648:Cytokine Receptor Common beta Subunit / Q000737:chemistry*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000737:chemistry / Q000502:physiology*; D015848:Interleukin-5 / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction / Q000502:physiology*
C115876:CSF2RB protein, human; D053648:Cytokine Receptor Common beta Subunit; D007377:Interleukin-3; D015848:Interleukin-5; D016178:Granulocyte-Macrophage Colony-Stimulating Factor