Circularly permuted interleukin 4 retains proliferative and binding activity

Cytokine
Robert J KreitmanI Pastan

Abstract

In human interleukin 4(IL-4), the carboxyl and amino termini of the 129 amino acid hormone are close to each other and this region is believed to be important for binding to the IL-4 receptor (IL-4r). We constructed plasmids encoding circularly permuted IL-4 mutants with the peptide Gly-Gly-Asn-Gly-Gly (GGNGG) joining the carboxyl to the amino terminus and with new amino and carboxyl termini elsewhere. Mutant IL-4(38-37) is composed of IL-4 residues 38-129 GGNGG and 1-37. Mutant IL-4(105-104) is composed of IL-4 residues 105-129, GGNGG and 1-104. IL-4(38-37) and IL-4(105-104) were purified from E. coli to near homogeneity and retained 50-100% of the binding and proliferative activity of IL-4, and in addition retained the ability to upregulate CD23 on Burkitt's lymphoma cells. Circular dichroism studies indicated that the tertiary structures of both IL-4(38-37) and IL-4(105-104) were retained, with the former molecule most similar to native IL-4. We conclude that while both native termini of IL-4 may be near its binding site, neither is required to be free for optimum activity.

Citations

Mar 31, 1999·Progress in Biophysics and Molecular Biology·R Jaenicke
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·R Graf, H K Schachman
Oct 10, 2006·The AAPS Journal·Robert J Kreitman
Jun 24, 1997·Proceedings of the National Academy of Sciences of the United States of America·J LiI Chaiken
May 9, 2000·The Journal of Biological Chemistry·Y OshimaR K Puri
Jun 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Y Oshima, R K Puri

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