Title : Structural insights into the interaction of
IL-33 with its
receptors
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
Output (sent_index, trigger,
protein,
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Output(Part-Of) (sent_index,
protein,
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*Output_Site_Fusion* (sent_index,
protein,
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