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

FEBS Letters

Siemion, Ignacy Z¹  Gaymes, Terry J²  Cebrat, Marek¹  Kay, John E² 

[1] Institute of Chemistry, University of Wroclaw, 50-383 Wroclaw, Poland;School of Biological Sciences, University of Sussex, Brighton BN1 9QG, UK

关键词: Cyclolinopeptide A;    Cyclophilin A;    Calcineurin;    T lymphocyte activation;    Peptidyl-prolyl cis-trans isomerase;   

DOI  :  10.1016/S0014-5793(97)01345-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown