3VA2

Crystal structure of human Interleukin-5 in complex with its alpha receptor

3VA2 の概要

• エントリーDOI: 10.2210/pdb3va2/pdb
• 分子名称: Interleukin-5, Interleukin-5 receptor subunit alpha (3 entities in total)
• 機能のキーワード: cytokine, eosinophilic, asthma, jak/stat, fibronectin iii-like (fn iii) domain, canonical cytokine receptor homology module (crm), b cell growth, ig secretion, eosinophils proliferation, cell surface, cytokine-cytokine receptor complex, cytokine/cytokine receptor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P05113; Membrane; Single-pass type I membrane protein: Q01344
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 63142.30

構造登録者

Kusano, S.,Kukimoto-Niino, M.,Shirouzu, M.,Yokoyama, S. (登録日: 2011-12-28, 公開日: 2012-07-25, 最終更新日: 2024-11-20)

主引用文献

Kusano, S.,Kukimoto-Niino, M.,Hino, N.,Ohsawa, N.,Ikutani, M.,Takaki, S.,Sakamoto, K.,Hara-Yokoyama, M.,Shirouzu, M.,Takatsu, K.,Yokoyama, S.
Structural basis of interleukin-5 dimer recognition by its alpha receptor
Protein Sci., 21:850-864, 2012

PubMed Abstract: Interleukin-5 (IL-5), a major hematopoietin, stimulates eosinophil proliferation, migration, and activation, which have been implicated in the pathogenesis of allergic inflammatory diseases, such as asthma. The specific IL-5 receptor (IL-5R) consists of the IL-5 receptor α subunit (IL-5RA) and the common receptor β subunit (βc). IL-5 binding to IL-5R on target cells induces rapid tyrosine phosphorylation and activation of various cellular proteins, including JAK1/JAK2 and STAT1/STAT5. Here, we report the crystal structure of dimeric IL-5 in complex with the IL-5RA extracellular domains. The structure revealed that IL-5RA sandwiches the IL-5 homodimer by three tandem domains, arranged in a "wrench-like" architecture. This association mode was confirmed for human cells expressing IL-5 and the full-length IL-5RA by applying expanded genetic code technology: protein photo-cross-linking experiments revealed that the two proteins interact with each other in vivo in the same manner as that in the crystal structure. Furthermore, a comparison with the previously reported, partial GM-CSF•GM-CSFRA•βc structure enabled us to propose complete structural models for the IL-5 and GM-CSF receptor complexes, and to identify the residues conferring the cytokine-specificities of IL-5RA and GM-CSFRA.

PubMed: 22528658
DOI: 10.1002/pro.2072

実験手法

X-RAY DIFFRACTION (2.703 Å)