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Publication Abstract from PubMed

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 hematopoietic 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 GM-CSF; and an IL-3-specific beta-subunit (betaIL-3). betaIL3 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. Here, we present the crystal structure of the betaIL-3 ectodomain at 3.45 A 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 to apo-betac, however, the ligand-binding interface of betaIL3 appears to pre-exist in a conformation receptive to IL-3 engagement. Molecular modelling of the IL-3:betaIL3 interface, in conjunction with previous mutational studies, suggests that divergent evolution of both betaIL3 and IL-3 underlies their unique capacity for direct interaction and specificity.

Crystal structure of the mouse interleukin-3 beta-receptor: insights into interleukin3 binding and receptor activation.,Carr PD, Ewens CL, Dai J, Ollis DL, Murphy JM, Jackson CJ, Young IG Biochem J. 2014 Aug 19. PMID:25137390^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.