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TitleFunctional Relevance of Interleukin-1 Receptor Inter-domain Flexibility for Cytokine Binding and Signaling.
Journal, issue, pagesStructure, Vol. 27, Issue 8, Page 1296-11307.e5, Year 2019
Publish dateAug 6, 2019
AuthorsJiwan Ge / Soumya G Remesh / Michal Hammel / Si Pan / Andrew D Mahan / Shuying Wang / Xinquan Wang /
PubMed AbstractThe 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.
External linksStructure / PubMed:31257107 / PubMed Central
MethodsSAS (X-ray synchrotron)
Structure data

SASDE29:
Interleukin-1 receptor accessory protein ectodomain with RI linker
Method: SAXS/SANS

SASDE39:
Interleukin-18 receptor accessory protein ectodomain with Rα linker
Method: SAXS/SANS

SASDE49:
Interleukin-1 receptor accessory protein ectodomains with ST2 linker
Method: SAXS/SANS

SASDE59:
Interleukin-1 receptor type 1, IL-1RI-ECD (Interleukin-1 receptor type 1, IL-1R-1)
Method: SAXS/SANS

SASDE69:
Interleukin-1 receptor type 2, IL-1RII-ECD (Interleukin-1 receptor type 2, IL-1R-2)
Method: SAXS/SANS

SASDE79:
Interleukin-18 receptor 1, IL-18Rα-ECD (Interleukin-18 receptor 1)
Method: SAXS/SANS

SASDE89:
Interleukin-1 receptor accessory protein ectodomain with RII linker
Method: SAXS/SANS

SASDEZ8:
Interleukin-18 receptor accessory protein, IL-18Rβ-ECD
Method: SAXS/SANS

Source
  • Homo sapiens (human)

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