MOLECULAR-CLONING AND OVEREXPRESSION OF THE HUMAN FK506-BINDING PROTEIN FKBP

THE potent immunosuppressive agent FK5061,2 is highly effective in preventing organ transplant rejection in humans3. Like cyclosporin A, FK506 inhibits the transcription of early T-cell activation genes4, apparently by modulating the activity of transcriptional regulators5 such as nuclear factor of activated T cells6. A remarkable finding is that the predominant binding proteins (immunophilins) for cyclosporin A and FK506, cyclophilin7-9 and FKBP10,11 respectively, are peptidyl-prolyl-cis-frans-isomerases that are potently and selectively inhibited by their respective ligands. Here we report the complementary DNA and derived amino-acid sequences of human FKBP from Jurkat cells and also the efficient overexpression in Escherichia coli of fully active, recombinant human FKBP. The human FKBP cDNA sequence shows significant similarity to an open reading frame in the Neisseria meningitidis genome12. © 1990 Nature Publishing Group.