Structure-function studies on recombinant human macrophage colony-stimulating factor (M-CSF).

摘要: Human macrophage colony-stimulating factor (M-CSF) is a homodimeric cytokine that member of structurally related family hormones defined by an unusual up-up-down-down alpha-helical bundle. To identify regions on the surface M-CSF might interact with receptor, single and double amino acid substitutions were introduced into truncated form human alpha site-directed mutagenesis, analogs purified characterized. Certain in region before helix A C decreased specific bioactivity correlated approximately equivalent reduction receptor affinity. The most dramatic change was observed analog which residues His-9 His-15 replaced alanines, resulting 9,100-fold decrease bioactivity. X-ray crystallographic analysis this H9A,H15A at resolution 2.5 revealed no significant changes structure other than expected new side chains 9 15. Analogs containing only one these two histidine exhibited 6- 1200-fold for H9A H15A mutations, respectively. It appears selected acids NH2-terminal possibly portions formed helices are significantly involved interactions receptor.