3QT2

Structure of a cytokine ligand-receptor complex

Summary for 3QT2

• Entry DOI: 10.2210/pdb3qt2/pdb
• Descriptor: Interleukin-5 receptor subunit alpha, Interleukin-5, beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: cytokine type i receptor fold, fibronectin type iii modules, four-helical bundle, cytokine, ligand-receptor complex, membrane, protein binding-immune system complex, protein binding/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 126908.43

Authors

Mueller, T.D.,Patino, E.,Kotzsch, A.,Saremba, S.,Nickel, J.,Schmitz, W.,Sebald, W. (deposition date: 2011-02-22, release date: 2012-02-01, Last modification date: 2024-10-30)

Primary citation

Patino, E.,Kotzsch, A.,Saremba, S.,Nickel, J.,Schmitz, W.,Sebald, W.,Mueller, T.D.
Structure Analysis of the IL-5 Ligand-Receptor Complex Reveals a Wrench-like Architecture for IL-5Ralpha.
Structure, 19:1864-1875, 2011

PubMed Abstract: Interleukin-5 (IL-5) is the key mediator for the function of eosinophil granulocytes, whose deregulation is characteristic of hypereosinophilic diseases and presumably contributes to allergic asthma. IL-5 signaling involves two transmembrane receptors, IL-5Rα and the common β chain, which upon formation of the ternary complex activate the JAK/STAT signaling cascade. To investigate the mechanism underlying ligand-receptor recognition, we determined the structure of IL-5 bound to the extracellular domain of IL-5Rα. IL-5 makes contact with all three fibronectin III-like domains of IL-5Rα, with the receptor architecture resembling a wrench. Mutagenesis data provide evidence that this wrench-like architecture is likely preformed. The structure demonstrates that for steric reasons, homodimeric IL-5 can bind only one receptor molecule, even though two equivalent receptor-binding sites exist. In regard to strong efforts being made to develop IL-5 antagonists for treating asthma and hypereosinophilic diseases, the advances in molecular understanding provided by this structure are of greatest value.

PubMed: 22153509
DOI: 10.1016/j.str.2011.08.015

Experimental method

X-RAY DIFFRACTION (2.55 Å)