RRC ID 34850
Author Tsutsumi N, Kimura T, Arita K, Ariyoshi M, Ohnishi H, Yamamoto T, Zuo X, Maenaka K, Park EY, Kondo N, Shirakawa M, Tochio H, Kato Z.
Title The structural basis for receptor recognition of human interleukin-18.
Journal Nat Commun
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.
Volume 5
Pages 5340
Published 2014-12-15
DOI 10.1038/ncomms6340
PII ncomms6340
PMID 25500532
PMC PMC4275594
MeSH Amino Acid Sequence Animals Baculoviridae / genetics Binding Sites Crystallography, X-Ray Gene Expression Humans Interleukin-1 Receptor Accessory Protein / chemistry Interleukin-1 Receptor Accessory Protein / genetics Interleukin-18 / chemistry* Interleukin-18 / genetics Interleukin-1beta / chemistry* Interleukin-1beta / genetics Molecular Sequence Data Mutation Protein Binding Protein Structure, Secondary Protein Structure, Tertiary Protein Subunits / chemistry* Protein Subunits / genetics Receptors, Interleukin / chemistry Receptors, Interleukin / genetics Receptors, Interleukin-18 / chemistry* Receptors, Interleukin-18 / genetics Recombinant Proteins / chemistry Recombinant Proteins / genetics Sequence Homology, Amino Acid Sf9 Cells Spodoptera
IF 12.121
Times Cited 42
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
DNA material Interleukin-18 Receptor alpha (extracellular domain) (RDB13431) Interleukin-18 Receptor beta (extracellular domain) (RDB13432).