4QQV

Extracellular domains of mouse IL-3 beta receptor

Summary for 4QQV

• Entry DOI: 10.2210/pdb4qqv/pdb
• Related: 2GYS
• Descriptor: Interleukin-3 receptor class 2 subunit beta, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: intertwined dimer, cytokine receptor, interleukin-3, signaling protein
• Biological source: Mus musculus (mouse)
• Cellular location: Membrane; Single-pass type I membrane protein: P26954
• Total number of polymer chains: 4
• Total formula weight: 192678.40

Authors

Jackson, C.J.,Young, I.G.,Murphy, J.M.,Carr, P.D.,Ewens, C.L.,Dai, J.,Ollis, D.L. (deposition date: 2014-06-30, release date: 2014-09-03, Last modification date: 2023-09-20)

Primary citation

Carr, P.D.,Ewens, C.L.,Dai, J.,Ollis, D.L.,Murphy, J.M.,Jackson, C.J.,Young, I.G.
Crystal structure of the mouse interleukin-3 beta-receptor: insights into interleukin-3 binding and receptor activation.
Biochem.J., 463:393-403, 2014

PubMed 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 α-subunit and a β-subunit, the principal signalling entity. In the mouse, two β-subunits have co-evolved: a common β-subunit (βc) shared between IL-3 and the related cytokines IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF); and an IL-3-specific β-subunit (βIL-3). βIL-3 differs from βc in its specificity for IL-3 and its capacity to bind IL-3 directly in the absence of an α-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 βIL-3 ectodomain at 3.45 Å (1 Å=0.1 nm) resolution. This structure provides the first evidence that βIL-3 adopts an arch-shaped intertwined homodimer with similar topology to the paralogous βc structure. In contrast with apo-βc, however, the ligand-binding interface of βIL-3 appears to pre-exist in a conformation receptive to IL-3 engagement. Molecular modelling of the IL-3-βIL-3 interface, in conjunction with previous mutational studies, suggests that divergent evolution of both βIL-3 and IL-3 underlies their unique capacity for direct interaction and specificity.

PubMed: 25137390
DOI: 10.1042/BJ20140863

Experimental method

X-RAY DIFFRACTION (3.45 Å)