Cyclolinopeptide A (CLA) mediates its immunosuppressive activity through cyclophilin-dependent calcineurin inactivation

Gaymes, Terry J, Cebrat, Marek, Siemion, Ignacy Z and Kay, John E (1997) Cyclolinopeptide A (CLA) mediates its immunosuppressive activity through cyclophilin-dependent calcineurin inactivation. FEBS Letters, 418(1-2), pp. 224-227. ISSN (print) 0014-5793

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Abstract

The immunosuppressive cyclic nonapeptide cyclolinopeptide A inhibits calcium-dependent, but not calcium-independent, activation of T lymphocytes comparably to the actions of cyclosporin A and FK506. The concentration required for complete inhibition, however, is 10 times higher than that of cyclosporin A. In addition, we demonstrate that calcineurin, a phosphatase which plays an important role in T lymphocyte signalling, is inhibited in vitro by cyclolinopeptide A by a mechanism dependent on the peptidyl-prolyl cis-trans isomerase (PPIase) cyclophilin A but not FKBP12. Direct binding of cyclolinopeptide A to cyclophilin A was confirmed using tryptophan fluorescence studies and PPIase assays. These results represent a third example of the production of a natural product that neutralises calcineurin by a mechanism dependent on the primary binding to a PPIase.

Item Type: Article
Research Area: Biological sciences
Faculty, School or Research Centre: Faculty of Science (until 2011) > School of Life Sciences
Related URLs:
Depositing User: Terry Gaymes
Date Deposited: 27 Apr 2017 15:22
Last Modified: 27 Apr 2017 15:22
URI: http://eprints.kingston.ac.uk/id/eprint/37288

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