2. Academic Validation
  3. Structural basis for the specific recognition of IL-18 by its alpha receptor

Structural basis for the specific recognition of IL-18 by its alpha receptor

  • FEBS Lett. 2014 Nov 3;588(21):3838-43. doi: 10.1016/j.febslet.2014.09.019.
Hui Wei 1,  Dongli Wang 1,  Yun Qian 1,  Xi Liu 1,  Shilong Fan 2,  Hsien-Sheng Yin 3,  Xinquan Wang 4
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
  • 4 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: [email protected].
PMID: 25261253 DOI: 10.1016/j.febslet.2014.09.019
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.

Keywords

Interleukin 18; Interleukin 18 receptor; Ligand-receptor recognition; X-ray structure.

Figures