論文 - 詳細
| RRC ID | 34850 |
|---|---|
| 著者 | 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. |
| タイトル | The structural basis for receptor recognition of human interleukin-18. |
| ジャーナル | 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. |
| 巻・号 | 5 |
| ページ | 5340 |
| 公開日 | 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 |
| 引用数 | 42 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| 遺伝子材料 | Interleukin-18 Receptor alpha (extracellular domain) (RDB13431) Interleukin-18 Receptor beta (extracellular domain) (RDB13432). |