7ZXK

Human IL-27 in complex with neutralizing SRF388 FAb fragment

7ZXK の概要

• エントリーDOI: 10.2210/pdb7zxk/pdb
• 関連するPDBエントリー: 7zg0
• 分子名称: Interleukin-27 subunit alpha, Interleukin-27 subunit beta, SRF388 Heavy Chain, ... (6 entities in total)
• 機能のキーワード: cytokine, heterodimer, neutralizing, antibody
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 192673.51

構造登録者

Bloch, Y.,Skladanowska, K.,Strand, J.,Welin, M.,Logan, D.,Hill, J.,Savvides, S.N. (登録日: 2022-05-21, 公開日: 2022-11-02, 最終更新日: 2024-11-06)

主引用文献

Skladanowska, K.,Bloch, Y.,Strand, J.,White, K.F.,Hua, J.,Aldridge, D.,Welin, M.,Logan, D.T.,Soete, A.,Merceron, R.,Murphy, C.,Provost, M.,Bazan, J.F.,Hunter, C.A.,Hill, J.A.,Savvides, S.N.
Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27.
Cell Rep, 41:111490-111490, 2022

PubMed Abstract: Interleukin-27 (IL-27) uniquely assembles p28 and EBI3 subunits to a heterodimeric cytokine that signals via IL-27Rα and gp130. To provide the structural framework for receptor activation by IL-27 and its emerging therapeutic targeting, we report here crystal structures of mouse IL-27 in complex with IL-27Rα and of human IL-27 in complex with SRF388, a monoclonal antibody undergoing clinical trials with oncology indications. One face of the helical p28 subunit interacts with EBI3, while the opposite face nestles into the interdomain elbow of IL-27Rα to juxtapose IL-27Rα to EBI3. This orients IL-27Rα for paired signaling with gp130, which only uses its immunoglobulin domain to bind to IL-27. Such a signaling complex is distinct from those mediated by IL-12 and IL-23. The SRF388 binding epitope on IL-27 overlaps with the IL-27Rα interaction site explaining its potent antagonistic properties. Collectively, our findings will facilitate the mechanistic interrogation, engineering, and therapeutic targeting of IL-27.

PubMed: 36261006
DOI: 10.1016/j.celrep.2022.111490

実験手法

X-RAY DIFFRACTION (2.2 Å)