Structural highlights
Publication Abstract from PubMedInterleukin-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-5Ralpha and the common beta 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-5Ralpha. IL-5 makes contact with all three fibronectin III-like domains of IL-5Ralpha, 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. Structure analysis of the IL-5 ligand-receptor complex reveals a wrench-like architecture for IL-5Ralpha.,Patino E, Kotzsch A, Saremba S, Nickel J, Schmitz W, Sebald W, Mueller TD Structure. 2011 Dec 7;19(12):1864-75. PMID:22153509[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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