Involvement of the Fourth α-Helix of Mouse Granulocyte-Macrophage Colony-Stimulating Factor in Binding to the α-Subunit of the Receptor Complex

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Abstract
Mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) proteins with substitutions for residues located within α-helix D were examined for biological activity and receptor binding properties. Alanine substitutions of the surface exposed positions indicated that several residues contribute to the ligand-receptor interface. Position K108 and particularly D102 appeared to dominate the binding epitope recognized by mGM-Rα. Several amino acid substitutions were made for K108 which reduced binding with concommitant losses in bioactivity. Substitutions for D102 resulted in binding affinities less than 0.1% that of the wild-type mGM-CSF and bioactivity decreased to 1.0%. Comparative analysis using high and low affinity binding conditions indicated that mGM-Rβ binding was unaffected by these mutations.