Interleukin 1β (IL-1β) is a key orchestrator of inflammation and host defense
that exerts its effects through IL-1 receptor type I (IL-1RI) and IL-1 receptor
accessory protein (IL-1RAcP). How IL-1RAcP is recruited by IL-1β-IL-1RI to form
the signaling-competent complex remains elusive. Here we present the crystal
structure of IL-1β bound to IL-1 receptor type II (IL-1RII) and IL-1RAcP.
IL-1β-IL-1RII generated a composite binding surface to recruit IL-1RAcP.
Biochemical analysis demonstrated that IL-1β-IL-1RI and IL-1β-IL-1RII
interacted similarly with IL-1RAcP. It also showed the importance of two loops
of IL-1 receptor antagonist (IL-1Ra) in determining its antagonism. Our results
provide a structural basis for assembly and activation of the IL-1 receptor and
offer a general cytokine-receptor architecture that governs the IL-1 family of
cytokines.
