ACID UNFOLDING AND SELF-ASSOCIATION OF RECOMBINANT ESCHERICHIA-COLI DERIVED HUMAN INTERFERON-GAMMA

The secondary and tertiary structure of recombinant human interferon 7, determined by farand near-UV circular dichroism, showed a transition from the native state to an unfolded state below pH 4.5. The acid unfolding was extensively studied at pH 3.5 as a function of NaCl concentration. Addition of 0.05-0.2 M NaCl to a pH 3.5 sample increased the amount of ß-sheet structure with no change in the amount of a-helix and also induced reversible self-association of interferon 7 to form large aggregates from the monomer. When samples at pH 3.5 were dialyzed against 0.1 M ammonium acetate (pH 6.9) to refold interferon 7, the samples that contained NaCl in acid formed aggregates upon dialysis while those without NaCl formed a dimer apparently identical with the starting protein (i.e., before acid treatment). Thus, the self-association of interferon 7 in acid is closely correlated with its aggregation behavior in 0.1 M ammonium acetate after removal of acid. © 1987, American Chemical Society. All rights reserved.