title: Structural basis for the specific recognition of IL-18 by its alpha receptor.
abstract: Interleukin 18 (IL-18), a member of the IL-1 family of cytokines, is an important regulator of innate and acquired immune responses. It signals through its ligand-binding primary receptor IL-18Rα and accessory receptor IL-18Rβ. Here we report the crystal structure of IL-18 with the ectodomain of IL-18Rα, which reveals the structural basis for their specific recognition. It confirms that surface charge complementarity determines the ligand-binding specificity of primary receptors in the IL-1 receptor family. We suggest that IL-18 signaling complex adopts an architecture similar to other agonistic cytokines and propose a general ligand-receptor assembly and activation model for the IL-1 family.
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wei
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Dongli
authors.initials: D
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Fan
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Hsien-Sheng
authors.initials: HS
authors.lastname: Yin
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing 100084, China; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. Electronic address: xinquanwang@mail.tsinghua.edu.cn.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D020382:Interleukin-18 / Q000737:chemistry* / Q000378:metabolism*; D053727:Interleukin-18 Receptor alpha Subunit / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D061987:Sf9 Cells; D018411:Spodoptera; D013379:Substrate Specificity; D013499:Surface Properties
chemical_list: D007375:Interleukin-1; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D008024:Ligands
keywords: Interleukin 18; Interleukin 18 receptor; Ligand-receptor recognition; X-ray structure