PDBsum entry 4qqv

Signaling protein

PDB id: 4qqv

Contents

Protein chains

399 a.a.

316 a.a.

Ligands

NAG ×4

PDB id:

4qqv

Name:

Signaling protein

Title:

Extracellular domains of mouse il-3 beta receptor

Structure:

Interleukin-3 receptor class 2 subunit beta. Chain: a, b, c, d. Fragment: extracellular domain (unp residues 23-438). Synonym: il-3 receptor class 2 subunit beta, il-3r class 2 subunit beta, colony-stimulating factor 2 receptor subunit beta-2, interleukin-3 receptor class ii beta chain, interleukin-3 cytokine receptor. Engineered: yes. Mutation: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: ai2ca, csf2rb2, il3r, il3rb2. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Resolution:

3.45Å R-factor: 0.206 R-free: 0.249

Authors:

C.J.Jackson,I.G.Young,J.M.Murphy,P.D.Carr,C.L.Ewens,J.Dai,D.L.Ollis

Key ref:

P.D.Carr et al. (2014). Crystal structure of the mouse interleukin-3 β-receptor: insights into interleukin-3 binding and receptor activation. Biochem J, 463, 393-403. PubMed id: 25137390 DOI: 10.1042/BJ20140863

Date:

30-Jun-14 Release date: 03-Sep-14

Protein chains

P26954  (IL3B2_MOUSE) -  Interleukin-3 receptor class 2 subunit beta from Mus musculus

Seq: 878 a.a.

Struc: 399 a.a.*

Protein chain

P26954  (IL3B2_MOUSE) -  Interleukin-3 receptor class 2 subunit beta from Mus musculus

Seq: 878 a.a.

Struc: 316 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1042/BJ20140863

Biochem J 463:393-403 (2014)

PubMed id: 25137390

Crystal structure of the mouse interleukin-3 β-receptor: insights into interleukin-3 binding and receptor activation.

P.D.Carr, C.L.Ewens, J.Dai, D.L.Ollis, J.M.Murphy, C.J.Jackson, I.G.Young.

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.