7U7N

IL-27 quaternary receptor signaling complex

7U7N の概要

• エントリーDOI: 10.2210/pdb7u7n/pdb
• EMDBエントリー: 26382
• 分子名称: Interleukin-27 receptor subunit alpha, Interleukin-6 receptor subunit beta, Interleukin-27 subunit beta, ... (8 entities in total)
• 機能のキーワード: cytokine receptor complex, il-27, cytokine
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 107155.30

構造登録者

Caveney, N.A.,Glassman, C.R.,Jude, K.M.,Tsutsumi, N.,Garcia, K.C. (登録日: 2022-03-07, 公開日: 2022-05-25, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.47 Å)