Interleukin-1 (IL-1) is an important mediator of inflammatory disease. The IL-1 family currently consists of two agonists, IL-1α and IL-lβ, and one antagonist, IL-1ra. Each of these molecules binds to the type I IL-1 receptor (IL1R)1. The binding of IL-1α or IL-1β to IL1R is an early step in IL-1 signal transduction and blocking this interaction may therefore be a useful target for the development of new drugs. Here we report the three-dimensional structure of IL-1β bound to the extracellular domain of IL1R (s-IL1R) at 2.5Å resolution. IL-1β binds to s-IL1R with a 1:1 stoichiometry. The crystal structure shows that s-IL1R consists of three immunoglobulin-like domains which wrap around IL-1β in a manner distinct from the structures of previously described cytokine–receptor complexes. The two receptor-binding regions on IL-1β identified by site-directed mutagenesis2,3 both contact the receptor: one binds to the first two domains of the receptor, while the other binds exclusively to the third domain.
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Vigers, G., Anderson, L., Caffes, P. et al. Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1β. Nature 386, 190–194 (1997). https://doi.org/10.1038/386190a0
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