The βc receptor family – Structural insights and their functional implications

• Published in: Cytokine (Philadelphia, Pa.) Vol. 74; no. 2; pp. 247 - 258
• Main Authors: Broughton, Sophie E., Nero, Tracy L., Dhagat, Urmi, Kan, Winnie L., Hercus, Timothy R., Tvorogov, Denis, Lopez, Angel F., Parker, Michael W.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2015
• Subjects: Animals; Beta common receptor; Cytokine Receptor Common beta Subunit - chemistry; Cytokine Receptor Common beta Subunit - immunology; Cytokines - chemistry; Cytokines - immunology; Granulocyte–macrophage colony stimulating factor; Humans; Inflammation; Interleukin-3; Interleukin-5; Protein Structure, Quaternary; Signal Transduction - immunology; Structure-Activity Relationship; Interleukin-3; Beta common receptor; Inflammation; Granulocyte–macrophage colony stimulating factor; Interleukin-5
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2015.02.005

•GM-CSF and IL-3 are pleiotropic cytokines with roles in health and disease.•New crystal structure of IL3Rα reveals novel open and closed conformations.•Membrane proximal and transmembrane domain movement likely to initiate signaling.
Granulocyte–macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and IL-5 are members of a small family of cytokines that share a beta receptor subunit (βc). These cytokines regulate the growth, differentiation, migration and effector function activities of many hematopoietic cells in bone marrow, blood and sites of inflammation. Excessive or aberrant signaling can result in chronic inflammatory conditions and myeloid leukemias. The crystal structures of the GM-CSF ternary complex, the IL-5 binary complex and the very recent IL-3 receptor alpha subunit build upon decades of structure–function studies, giving new insights into cytokine–receptor specificity and signal transduction. Selective modulation of receptor function is now a real possibility and the structures of the βc receptor family are being used to discover novel and disease-specific therapeutics.