4KC3

Cytokine/receptor binary complex

Summary for 4KC3

• Entry DOI: 10.2210/pdb4kc3/pdb
• Descriptor: Interleukin-33, Interleukin-1 receptor-like 1, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: beta-trefoil, ig-like domain, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 53876.01

Authors

Liu, X.,Wang, X.Q. (deposition date: 2013-04-24, release date: 2013-08-28, Last modification date: 2024-10-16)

Primary citation

Liu, X.,Hammel, M.,He, Y.,Tainer, J.A.,Jeng, U.S.,Zhang, L.,Wang, S.,Wang, X.
Structural insights into the interaction of IL-33 with its receptors.
Proc.Natl.Acad.Sci.USA, 110:14918-14923, 2013

PubMed Abstract: Interleukin (IL)-33 is an important member of the IL-1 family that has pleiotropic activities in innate and adaptive immune responses in host defense and disease. It signals through its ligand-binding primary receptor ST2 and IL-1 receptor accessory protein (IL-1RAcP), both of which are members of the IL-1 receptor family. To clarify the interaction of IL-33 with its receptors, we determined the crystal structure of IL-33 in complex with the ectodomain of ST2 at a resolution of 3.27 Å. Coupled with structure-based mutagenesis and binding assay, the structural results define the molecular mechanism by which ST2 specifically recognizes IL-33. Structural comparison with other ligand-receptor complexes in the IL-1 family indicates that surface-charge complementarity is critical in determining ligand-binding specificity of IL-1 primary receptors. Combined crystallography and small-angle X-ray-scattering studies reveal that ST2 possesses hinge flexibility between the D3 domain and D1D2 module, whereas IL-1RAcP exhibits a rigid conformation in the unbound state in solution. The molecular flexibility of ST2 provides structural insights into domain-level conformational change of IL-1 primary receptors upon ligand binding, and the rigidity of IL-1RAcP explains its inability to bind ligands directly. The solution architecture of IL-33-ST2-IL-1RAcP complex from small-angle X-ray-scattering analysis resembles IL-1β-IL-1RII-IL-1RAcP and IL-1β-IL-1RI-IL-1RAcP crystal structures. The collective results confer IL-33 structure-function relationships, supporting and extending a general model for ligand-receptor assembly and activation in the IL-1 family.

PubMed: 23980170
DOI: 10.1073/pnas.1308651110

Experimental method

X-RAY DIFFRACTION (3.2702 Å)