Site-specific mutagenesis of the human interleukin-1 beta gene: the role of arginine residue at the N-terminal region |
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Authors: | T Kamogashira M Sakaguchi Y Ohmoto K Mizuno R Shimizu K Nagamura S Nakai Y Masui Y Hirai |
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Institution: | Laboratories of Cellular Technology, Otsuka Pharmaceutical Co., Ltd., Tokushima. |
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Abstract: | 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 beta (IL-1 beta) consisting of 153 amino acids. The truncated mutants showed that at least 147 amino acids (numbers 4-150) in IL-1 beta are necessary for the exertion of biological activity. When we changed the arginine at the 4th position (Arg4) in IL-1 beta 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 greater than Gln4 greater than Gly4 = des-Arg4 greater than Asp4. Our results demonstrate that the arginine residue at the 4th position in IL-1 beta is important, but not essential, for IL-1 beta to exhibit its biological and receptor binding activities, and the positive charge at this site plays a key role for IL-1 beta to exert the activities. |
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