7Z0L

IL-27 signalling complex

Summary for 7Z0L

• Entry DOI: 10.2210/pdb7z0l/pdb
• EMDB information: 14427
• Descriptor: Interleukin-6 receptor subunit beta, Interleukin-27 subunit beta,Interleukin-27 subunit alpha, Interleukin-27 receptor subunit alpha, ... (5 entities in total)
• Functional Keywords: cytokine, immunosuppression, ebi3, il-27r-alpha, gp130, p28.
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 3
• Total formula weight: 113922.12

Authors

Jin, Y.,Gardner, S.,Bubeck, D. (deposition date: 2022-02-23, release date: 2022-07-27, Last modification date: 2024-11-06)

Primary citation

Jin, Y.,Fyfe, P.K.,Gardner, S.,Wilmes, S.,Bubeck, D.,Moraga, I.
Structural insights into the assembly and activation of the IL-27 signaling complex.
Embo Rep., 23:e55450-e55450, 2022

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 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.

PubMed: 35920255
DOI: 10.15252/embr.202255450

Experimental method

ELECTRON MICROSCOPY (4 Å)