Structural insights into the assembly and activation of the IL‐27 signaling complex

By Yibo Jin, Paul Fyfe, S. Gardner, S. Wilmes, D. Bubeck, Ignacio Moraga. 2022

32 citations recorded by the source corpus.

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.

Subfields: Immunology, Oncology

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Citations in the corpus

• AlphaFold2 and its applications in the fields of biology and medicine (2023, methodology): “Jin et al. 72 solved the structure of interleukin (IL) − 27 signal complex by using cryo-EM with the aid of AF2 prediction, through which they revealed a new mechanism for the assembly and activation of IL-27 receptor recognition complex.”