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Title: The structural basis for receptor recognition of human interleukin-18

Interleukin (IL)-18 is a proinflammatory cytokine that belongs to the IL-1 family and plays an important role in inflammation. The uncontrolled release of this cytokine is associated with severe chronic inflammatory disease. IL-18 forms a signalling complex with the IL-18 receptor α (Rα) and β (Rβ) chains at the plasma membrane, which induces multiple inflammatory cytokines. Here, we present a crystal structure of human IL-18 bound to the two receptor extracellular domains. Generally, the receptors’ recognition mode for IL-18 is similar to IL-1β; however, certain notable differences were observed. The architecture of the IL-18 receptor second domain (D2) is unique among the other IL-1R family members, which presumably distinguishes them from the IL-1 receptors that exhibit a more promiscuous ligand recognition mode. The structures and associated biochemical and cellular data should aid in developing novel drugs to neutralize IL-8 activity.
 [1] ;  [2] ;  [3] ;  [1] ;  [2] ;  [2] ;  [4] ;  [5] ;  [6] ;  [2] ;  [7] ;  [1] ;  [2]
  1. Kyoto Univ., Kyoto (Japan)
  2. Gifu Univ., Yanagido (Japan)
  3. Yokohama City Univ., Kanagawa (Japan)
  4. Argonne National Lab. (ANL), Argonne, IL (United States)
  5. Hokkaido Univ., Sapporo (Japan)
  6. Shizuoka Univ., Shizuoka (Japan)
  7. Kyoto Univ., Kyoto (Japan); Japan Sciences and Technology Agency, Tokyo (Japan)
Publication Date:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2041-1723
Nature Publishing Group
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; biological sciences; biochemistry; immunology
OSTI Identifier:
Alternate Identifier(s):
OSTI ID: 1241361