title: Structural insights into the assembly and activation of IL-1β with its receptors.
abstract: 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.
authors.affiliation: Center for Structural Biology, School of Life Sciences, Ministry of Education Key Laboratory of Bioinformatics, Tsinghua University, Beijing, China.
authors.forename: Dongli
authors.initials: D
authors.lastname: Wang
authors.forename: Senyan
authors.initials: S
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Kunrong
authors.initials: K
authors.lastname: Mei
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D003461:Crystallography; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000737:chemistry; D053577:Interleukin-1 Receptor Accessory Protein / Q000737:chemistry* / Q000378:metabolism; D053583:Interleukin-1beta / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D053574:Receptors, Interleukin-1 Type II / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053577:Interleukin-1 Receptor Accessory Protein; D053583:Interleukin-1beta; D053574:Receptors, Interleukin-1 Type II
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