6O4P

The crystal structure of the interleukin 11 alpha receptor

6O4P の概要

• エントリーDOI: 10.2210/pdb6o4p/pdb
• 分子名称: Interleukin-11 receptor subunit alpha, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: cytokine, interleukin, receptor, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78874.29

構造登録者

Aizel, K.,Metcalfe, R.D.,Griffin, M.D.W. (登録日: 2019-02-28, 公開日: 2020-05-06, 最終更新日: 2024-11-20)

主引用文献

Metcalfe, R.D.,Aizel, K.,Zlatic, C.O.,Nguyen, P.M.,Morton, C.J.,Lio, D.S.,Cheng, H.C.,Dobson, R.C.J.,Parker, M.W.,Gooley, P.R.,Putoczki, T.L.,Griffin, M.D.W.
The structure of the extracellular domains of human interleukin 11 alpha receptor reveals mechanisms of cytokine engagement.
J.Biol.Chem., 295:8285-8301, 2020

PubMed Abstract: Interleukin (IL) 11 activates multiple intracellular signaling pathways by forming a complex with its cell surface α-receptor, IL-11Rα, and the β-subunit receptor, gp130. Dysregulated IL-11 signaling has been implicated in several diseases, including some cancers and fibrosis. Mutations in IL-11Rα that reduce signaling are also associated with hereditary cranial malformations. Here we present the first crystal structure of the extracellular domains of human IL-11Rα and a structure of human IL-11 that reveals previously unresolved detail. Disease-associated mutations in IL-11Rα are generally distal to putative ligand-binding sites. Molecular dynamics simulations showed that specific mutations destabilize IL-11Rα and may have indirect effects on the cytokine-binding region. We show that IL-11 and IL-11Rα form a 1:1 complex with nanomolar affinity and present a model of the complex. Our results suggest that the thermodynamic and structural mechanisms of complex formation between IL-11 and IL-11Rα differ substantially from those previously reported for similar cytokines. This work reveals key determinants of the engagement of IL-11 by IL-11Rα that may be exploited in the development of strategies to modulate formation of the IL-11-IL-11Rα complex.

PubMed: 32332100
DOI: 10.1074/jbc.RA119.012351

実験手法

X-RAY DIFFRACTION (3.429 Å)