STRUCTURE-ACTIVITY STUDIES OF THE CYTOKINE MACROPHAGE-MIGRATION INHIBITORY FACTOR (MIF) REVEAL A CRITICAL ROLE FOR ITS CARBOXY-TERMINUS

Carboxy-truncated mutants of human MIF (MIF(1-104) and MIF(1-109)) wer e used in structure activity studies, CD spectroscopy revealed an over all structural similarity between the mutants and MIF, Denaturant-indu ced unfolding demonstrated that the C-terminus contributed significant ly to the conformational stability of MIF. This appears to be due to t he formation of two C-terminal beta-strands, The mutants were enzymati cally active, exhibiting half of the enzymatic redox activity of MIF. However, immunological analysis showed that deletion of both 5 and 10 C-terminal residues resulted in loss of the macrophage activating prop erties of MIF, providing functional evidence that the C-terminus is im portant for immunological activity and trimer formation. A more detail ed study of the C-terminus may assist in identifying the molecular bas is for the immunological and enzymatic activities of MIF. (C) 1997 Fed eration of European Biochemical Societies.