The structural basis for receptor recognition of human interleukin-18.

Abstract

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-18 activity.

• Authors: Naotaka Tsutsumi, Takeshi Kimura, Kyohei Arita, Mariko Ariyoshi, Hidenori Ohnishi, Takahiro Yamamoto, Xiaobing Zuo, Katsumi Maenaka, Enoch Y Park, Naomi Kondo, Masahiro Shirakawa, Hidehito Tochio, Zenichiro Kato
• Journal: Nature communications (Nat Commun) Vol. 5 Pg. 5340 (Dec 15 2014) ISSN: 2041-1723 [Electronic] England
• PMID: 25500532 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• IL18 protein, human
• IL1RAP protein, human
• Interleukin-1 Receptor Accessory Protein
• Interleukin-18
• Interleukin-1beta
• Protein Subunits
• Receptors, Interleukin
• Receptors, Interleukin-18
• Recombinant Proteins
• interleukin-36 receptor, human

Topics

• Amino Acid Sequence
• Animals
• Baculoviridae (genetics)
• Binding Sites
• Crystallography, X-Ray
• Gene Expression
• Humans
• Interleukin-1 Receptor Accessory Protein (chemistry, genetics)
• Interleukin-18 (chemistry, genetics)
• Interleukin-1beta (chemistry, genetics)
• Molecular Sequence Data
• Mutation
• Protein Binding
• Protein Structure, Secondary
• Protein Structure, Tertiary
• Protein Subunits (chemistry, genetics)
• Receptors, Interleukin (chemistry, genetics)
• Receptors, Interleukin-18 (chemistry, genetics)
• Recombinant Proteins (chemistry, genetics)
• Sequence Homology, Amino Acid
• Sf9 Cells
• Spodoptera