Cyclophilin: A Specific Cytosolic Binding Protein for Cyclosporin A

American Association for the Advancement of Science (AAAS) - Tập 226 Số 4674 - Trang 544-547 - 1984
Robert E. Handschumacher1, Matthew W. Harding1, Jeffrey S. Rice1, Rhett J Drugge1, David W. Speicher2
1Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510
2Protein Chemistry Laboratory, Department of Pathology, Yale University School of Medicine

Tóm tắt

Cyclophilin, a specific cytosolic binding protein responsible for the concentration of the immunosuppressant cyclosporin A by lymphoid cells, was purified to homogeneity from bovine thymocytes. Cation-exchange high-performance liquid chromatography resolved a major and minor cyclophilin species that bind cyclosporin A with a dissociation constant of about 2 × 10 -7 moles per liter and specific activities of 77 and 67 micrograms per milligram of protein, respectively. Both cyclophilin species have an apparent molecular weight of 15,000, an isoelectric point of 9.6, and nearly identical amino acid compositions. A portion of the NH 2 -terminal amino acid sequence of the major species was determined. The cyclosporin A-binding activity of cyclophilin is sulfhydryl dependent, unstable at 56°C and at p H 4 or 9.5, and sensitive to trypsin but not to chymotrypsin digestion. Cyclophilin specifically binds a series of cyclosporin analogs in proportion to their activity in a mixed lymphocyte reaction. Isolation of cyclophilin from the cytosol of thymocytes suggests that the immunosuppressive activity of cyclosporin A is mediated by an intracellular mechanism, not by a membrane-associated mechanism.

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American Association for the Advancement of Science (AAAS)

Tập 226 Số 4674

544-547

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