ISOLATION AND SEQUENCE OF AN FK506-BINDING PROTEIN FROM NEUROSPORA-CRASSA WHICH CATALYZES PROTEIN FOLDING

SLOW protein-folding reactions are accelerated by a prolyl cis/trans isomerase isolated from porcine kidney1,2 which is identical3,4 to cyclophilin5, a protein that is probably the cellular receptor for the immunosuppressant cyclosporin A6,14. Catalysis probably involves the isomerization of prolyl peptide bonds in the folding protein chains. Cyclosporin A inhibits folding catalysis by cyclophilin4. Here we report the isolation, cloning, sequencing and expression of another protein with prolyl isomerase activity from Neurospora crassa which is unrelated to cyclophilin and which also catalyses slow steps in protein folding. This protein does, however, show sequence similarity to a human protein7-9 that binds to another, recently discovered immunosuppressive drug, FK506 (ref. 10). Moreover, it shares 39% identity with the carboxy-terminal 114 residues of a cell-surface protein from the bacterium Legionella pneumophila, the causative agent of Legionnaires' disease11,12. Catalysis of folding by the FK506-binding protein from N. crassa is inhibited by FK506, but not by cyclosporin A. Thus, at least two different classes of conformationally active enzymes (conformases13) exist that catalyse slow steps in protein folding. Both occur in a wide variety of cells and are inhibited by immunosupressive drugs. © 1990 Nature Publishing Group.