Citation

BibTex format

@article{Bubeck:2022,
author = {Bubeck, D and Jin, Y and Fyfe, PK and Gardner, S and Wilmes, S and Moraga, I},
journal = {EMBO Reports},
title = {Structural insights into the assembly and activation of the IL-27 signalling complex},
url = {http://hdl.handle.net/10044/1/98306},
year = {2022}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Interleukin 27 (IL-27) is a heterodimeric cytokine that elicits potent immuno-suppressive responses. Comprised of EBI3 and p28 subunits, IL-27 binds GP130 and IL-27Rα receptor chains to activate the JAK/STAT signalling 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 AlphaFold2 modelling 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 signalling. 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.
AU - Bubeck,D
AU - Jin,Y
AU - Fyfe,PK
AU - Gardner,S
AU - Wilmes,S
AU - Moraga,I
PY - 2022///
SN - 1469-221X
TI - Structural insights into the assembly and activation of the IL-27 signalling complex
T2 - EMBO Reports
UR - http://hdl.handle.net/10044/1/98306
ER -