7U7N

IL-27 quaternary receptor signaling complex

Summary for 7U7N

• Entry DOI: 10.2210/pdb7u7n/pdb
• EMDB information: 26382
• Descriptor: Interleukin-27 receptor subunit alpha, Interleukin-6 receptor subunit beta, Interleukin-27 subunit beta, ... (8 entities in total)
• Functional Keywords: cytokine receptor complex, il-27, cytokine
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 107155.30

Authors

Caveney, N.A.,Glassman, C.R.,Jude, K.M.,Tsutsumi, N.,Garcia, K.C. (deposition date: 2022-03-07, release date: 2022-05-25)

Primary citation

Caveney, N.A.,Glassman, C.R.,Jude, K.M.,Tsutsumi, N.,Garcia, K.C.
Structure of the IL-27 quaternary receptor signaling complex.
Elife, 11:-, 2022

PubMed Abstract: Interleukin 27 (IL-27) is a heterodimeric cytokine that functions to constrain T cell-mediated inflammation and plays an important role in immune homeostasis. Binding of IL-27 to cell surface receptors, IL-27Rα and gp130, results in activation of receptor-associated Janus Kinases and nuclear translocation of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT3 transcription factors. Despite the emerging therapeutic importance of this cytokine axis in cancer and autoimmunity, a molecular blueprint of the IL-27 receptor signaling complex, and its relation to other gp130/IL-12 family cytokines, is currently unclear. We used cryogenic-electron microscopy to determine the quaternary structure of IL-27, composed of p28 and Epstein-Barr Virus-Induced 3 (Ebi3) subunits, bound to receptors, IL-27Rα and gp130. The resulting 3.47 Å resolution structure revealed a three-site assembly mechanism nucleated by the central p28 subunit of the cytokine. The overall topology and molecular details of this binding are reminiscent of IL-6 but distinct from related heterodimeric cytokines IL-12 and IL-23. These results indicate distinct receptor assembly mechanisms used by heterodimeric cytokines with important consequences for targeted agonism and antagonism of IL-27 signaling.

PubMed: 35579417
DOI: 10.7554/eLife.78463

Experimental method

ELECTRON MICROSCOPY (3.47 Å)