Isolation and sequence of an FK506-binding protein from N. crassa which catalyses protein folding.
Slow protein-folding reactions are accelerated by a prolyl cis/trans isomerase isolated from porcine kidney which is identical to cyclophilin, a protein that is probably the cellular receptor for the immunosuppressant cyclosporin A. Catalysis probably involves the isomerization of prolyl peptide bonds in the folding protein chains. Cyclosporin A inhibits folding catalysis by cyclophilin. 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 protein that binds to another, recently discovered immunosuppressive drug, FK506. 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' disease. 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 (conformases) exist that catalyse slow steps in protein folding. Both occur in a wide variety of cells and are inhibited by immunosuppressive drugs.
Institut für Physiologische Chemie der Universität München, FRG.
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Tropschug
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Wachter
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Mayer
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Schönbrunner
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Schmid
D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors / Q000302:isolation & purification* / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002384:Catalysis; D003001:Cloning, Molecular; D003524:Cyclosporins / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D007166:Immunosuppressive Agents / Q000378:metabolism* / Q000494:pharmacology; D007875:Legionella / Q000032:analysis; D008969:Molecular Sequence Data; D009491:Neurospora / Q000032:analysis*; D009492:Neurospora crassa / Q000032:analysis*; D019696:Peptidylprolyl Isomerase; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D004247:DNA; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus