Structural insights into the assembly and activation of IL-1β with its receptors
- 29 August 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 11 (10), 905-911
- https://doi.org/10.1038/ni.1925
Abstract
The proinflammatory cytokine IL-1β signals via a heterodimeric receptor composed of the receptor IL-1RI and the accessory protein IL-1RAcP. Wang and colleagues solve the ligand-receptor structure and explain how antagonist interactions differ. 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.Keywords
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