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| Title | Structural insights into the assembly and activation of the IL-27 signaling complex. |
|---|---|
| Journal, issue, pages | EMBO Rep, Vol. 23, Issue 10, Page e55450, Year 2022 |
| Publish date | Oct 6, 2022 |
 Authors | Yibo Jin / Paul K Fyfe / Scott Gardner / Stephan Wilmes / Doryen Bubeck / Ignacio Moraga /  |
| PubMed Abstract | Interleukin 27 (IL-27) is a heterodimeric cytokine that elicits potent immunosuppressive responses. Comprised of EBI3 and p28 subunits, IL-27 binds GP130 and IL-27Rα receptor chains to activate the ...Interleukin 27 (IL-27) is a heterodimeric cytokine that elicits potent immunosuppressive responses. Comprised of EBI3 and p28 subunits, IL-27 binds GP130 and IL-27Rα receptor chains to activate the JAK/STAT signaling cascade. However, how these receptors recognize IL-27 and form a complex capable of phosphorylating JAK proteins remains unclear. Here, we used cryo electron microscopy (cryoEM) and AlphaFold modeling to solve the structure of the IL-27 receptor recognition complex. Our data show how IL-27 serves as a bridge connecting IL-27Rα (domains 1-2) with GP130 (domains 1-3) to initiate signaling. While both receptors contact the p28 component of the heterodimeric cytokine, EBI3 stabilizes the complex by binding a positively charged surface of IL-27Rα and Domain 1 of GP130. We find that assembly of the IL-27 receptor recognition complex is distinct from both IL-12 and IL-6 cytokine families and provides a mechanistic blueprint for tuning IL-27 pleiotropic actions. |
 External links | EMBO Rep / PubMed:35920255 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.0 Å |
| Structure data | EMDB-14427, PDB-7z0l: |
| Chemicals |  ChemComp-NAG: |
| Source |
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 Keywords |  CYTOKINE / immunosuppression / EBI3 / IL-27R-alpha / gp130 / p28. |
