Publication Abstract from PubMed
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 alpha subunit (IL-5RA) and the common receptor beta subunit (betac). 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*betac 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.
Structural basis of interleukin-5 dimer recognition by its alpha receptor.,Kusano S, Kukimoto-Niino M, Hino N, Ohsawa N, Ikutani M, Takaki S, Sakamoto K, Hara-Yokoyama M, Shirouzu M, Takatsu K, Yokoyama S Protein Sci. 2012 Jun;21(6):850-64. doi: 10.1002/pro.2072. Epub 2012 Apr 23. PMID:22528658[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
