EFFECT OF TOPOGRAPHY OF THE SIGNAL PROTEA SE CLEAVAGE SITE ON THE EFFICIENCY OF SECRETION OF HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INTO PERIPLASM OF ESCHERICHIA-COLI CELL

Synthesis of an artificial gene encoding the signal peptide of the Yer sinia pestis capsule antigen (Caf1) was accomplished. A set of plasmid s coding for hybrid proteins in which a modified sequence of the Caf1 signal peptide is connected to the amino acid sequence of the mature g ranulocyte-macrophage colony stimulating factor (GM-CSF) were construc ted. Topography of the cleavage site of signal proteases was studied. The presence of an arginine residue within the N-terminal part of the mature human GM-CSF was shown to hinder the proper processing and tran slocation of the precursor through periplasmic membrane. A number of E . coli strains secreting biologically active mutants of human GM-CSF w ere obtained.