+検索条件
-Structure paper
タイトル | Functional Relevance of Interleukin-1 Receptor Inter-domain Flexibility for Cytokine Binding and Signaling. |
---|---|
ジャーナル・号・ページ | Structure, Vol. 27, Issue 8, Page 1296-11307.e5, Year 2019 |
掲載日 | 2019年8月6日 |
著者 | Jiwan Ge / Soumya G Remesh / Michal Hammel / Si Pan / Andrew D Mahan / Shuying Wang / Xinquan Wang / |
PubMed 要旨 | The interleukin 1 (IL-1) receptor family, whose members contain three immunoglobulin-like domains (D1-D3) in the extracellular region, is responsible for transmitting pleiotropic signals of IL-1 ...The interleukin 1 (IL-1) receptor family, whose members contain three immunoglobulin-like domains (D1-D3) in the extracellular region, is responsible for transmitting pleiotropic signals of IL-1 cytokines. The inter-domain flexibility of IL-1 receptors and its functional roles have not been fully elucidated. In this study, we used small-angle X-ray scattering to show that ligand-binding primary receptors and co-receptors in the family all have inherent inter-domain flexibility due to the D2/D3 linker. Variants of the IL-1RAcP and IL-18Rβ co-receptors with mutated D2/D3 linkers cannot form a cytokine-receptor complex and mediate signaling. Our analysis further revealed that these mutated co-receptors exhibited a changed conformational ensemble, suggesting that loss of function is due to the alteration of receptor dynamics. Taken together, our results demonstrate that the D2/D3 linker is a critical functional determinant of IL-1 receptor and underscore the important roles of the inter-domain flexibility in cytokine/receptor binding and signaling. |
リンク | Structure / PubMed:31257107 / PubMed Central |
手法 | SAS (X-ray synchrotron) |
構造データ | SASDE29: SASDE39: SASDE49: SASDE59: SASDE69: SASDE79: SASDE89: SASDEZ8: |
由来 |
|