Crystal structure of the mouse interleukin-3 beta-receptor: insights into interleukin-3 binding and receptor activation
- Author(s)
- Carr, PD; Ewens, CL; Dai, J; Ollis, DL; Murphy, JM; Jackson, CJ; Young, IG;
- Details
- Publication Year 2014-11-01,Volume 463,Issue #3,Page 393-403
- Journal Title
- Biochem J
- Publication Type
- Journal Article
- Abstract
- Interleukin-3 (IL-3) is a cytokine secreted by mast cells and activated T-cells known to be an important regulator of differentiation, survival, proliferation and activation of a range of haemopoietic lineages. The effects of IL-3 on target cells are mediated by a transmembrane receptor system composed of a cytokine-specific alpha-subunit and a beta-subunit, the principal signalling entity. In the mouse, two beta-subunits have co-evolved: a common beta-subunit (betac) shared between IL-3 and the related cytokines IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF); and an IL-3-specific beta-subunit (betaIL-3). betaIL-3 differs from betac in its specificity for IL-3 and its capacity to bind IL-3 directly in the absence of an alpha-subunit, and, in the absence of structural information, the basis for these properties has remained enigmatic. In the present study, we have solved the crystal structure of the betaIL-3 ectodomain at 3.45 A (1 A=0.1 nm) resolution. This structure provides the first evidence that betaIL-3 adopts an arch-shaped intertwined homodimer with similar topology to the paralogous betac structure. In contrast with apo-betac, however, the ligand-binding interface of betaIL-3 appears to pre-exist in a conformation receptive to IL-3 engagement. Molecular modelling of the IL-3-betaIL-3 interface, in conjunction with previous mutational studies, suggests that divergent evolution of both betaIL-3 and IL-3 underlies their unique capacity for direct interaction and specificity.
- Publisher
- Portland Press
- Keywords
- cytokine receptor, ectodomain, granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), interleukin 5 (IL-5), surface entropy reduction
- Research Division(s)
- Cell Signalling And Cell Death
- Publisher's Version
- https://doi.org/10.1042/BJ20140863
- Terms of Use/Rights Notice
- © The Authors Journal compilation © 2014 Biochemical Society
Creation Date: 2014-11-14 01:50:10
Last Modified: 2015-05-25 03:59:27