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TitleStructure of the IL-27 quaternary receptor signaling complex.
Journal, issue, pagesElife, Vol. 11, Year 2022
Publish dateMay 17, 2022
AuthorsNathanael A Caveney / Caleb R Glassman / Kevin M Jude / Naotaka Tsutsumi / K Christopher Garcia /
PubMed AbstractInterleukin 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 ...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.
External linksElife / PubMed:35579417 / PubMed Central
MethodsEM (single particle)
Resolution3.47 Å
Structure data

26382

7u7n

EMDB-26382, PDB-7u7n:
IL-27 quaternary receptor signaling complex
Method: EM (single particle) / Resolution: 3.47 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
KeywordsCYTOKINE / Cytokine Receptor Complex / IL-27

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