Site-specific mutagenesis of the human interleukin-1 beta gene: the role of arginine residue at the N-terminal region

Using the expression system for site-specific mutagenesis in Escherichia coli, we have made deletion mutants at the N-terminal or C-terminal region of human interleukin-1/7 (IL-1/9) consisting of 153 amino acids. The truncated mutants showed that at least 147 amino acids (numbers 4-150) in IL-1/9 are necessary for the exertion of biological activity. When we changed the arginine at the 4th position (Arg4) in IL-1/? to other specific amino acids, there was a marked difference in the relative extent of biological and receptor binding activities among the mutants. The order of the mutants was Arg4 = Lys4>Gln"> Gly4 = des-Arg4> Asp4. Our results demonstrate that the arginine residue at the 4th position in IL-1/9 is important, but not essential, for IL-1 # to exhibit its biological and receptor binding activities, and the positive charge at this site plays a key role for IL-1/? to exert the activities. Human interleukin-1 (IL-1) was first defined as a lympho-cyte activating factor (LAF) produced by monocyte/macro-phages (1), and it has become evident that the IL-1 activities are produced by several other cell types (2). IL-