Journal
EMBO REPORTS
Volume 23, Issue 10, Pages -Publisher
WILEY
DOI: 10.15252/embr.202255450
Keywords
cytokine; IL-27; cryo electron microscopy; GP130
Categories
Funding
- Wellcome-Trust [202323/Z/16/Z]
- ERC-206-STG grant
- Wellcome Trust
- Medical Research Council
- BBSRC
- Wellcome Trust [202323/Z/16/Z] Funding Source: Wellcome Trust
Ask authors/readers for more resources
IL-27 is an important cytokine that induces immunosuppressive responses. The study reveals the structure of the IL-27 receptor recognition complex and provides insights into the mechanism of IL-27 signaling. These findings contribute to a better understanding of IL-27's function and regulation.
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-27R alpha 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-27R alpha (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-27R alpha 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available