Histidine-367 of the human common β chain of the receptor is critical for high-affinity binding of human granulocyte-macrophage colony-stimulating factor

Abstract

High-affinity receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3, and interleukin 5 consist of ligand-specific α chains (low-affinity subunits) and a common β chain (β(c)) that converts each complex to a high-affinity form. Although β(c) alone has no detectable cytokine-binding activity, amino acid substitutions for Glu-21 of human GM- CSF significantly reduce high-affinity but not low-affinity binding, implying that β(c) interacts directly with GM-CSF during formation of the high- affinity receptor but only in the presence of the α chain. A potential GM- CSF-binding determinant was identified in the second hemopoietin domain of β(c), and the role of indiv..