RECOMBINANT HUMAN IL-6 EXPRESSED IN ESCHERICHIA-COLI UNDERGOES SELECTIVE N-TERMINAL DEGRADATION - EVIDENCE THAT THE PROTEIN CONSISTS OF A STABLE CORE AND A NONESSENTIAL FLEXIBLE N-TERMINAL

A synthetic gene for human interleukin-6 has been expressed in E. coli. The protein has been purified and renatured and has the same activity as natural human IL-6 using the 7TD1 cell proliferation assay. The protein undergoes specific cleavage by a thiol protease, yielding two new N-termini at Arg-9 and His- 1 5. The truncated proteins retain full biological activity. The degradation results in the loss of sharp amide resonances in the H-1-NMR spectrum, and little change to the ultraviolet CD spectrum. Several amino acid type assignments could be made for these sharp amides using a DQF-COSY 2D-NMR experiment. The N-terminal 15 amino acids exist as a flexible, random coil, attached to a central structure.