Mapping of the immunophilin-immunosuppressant site of interaction on calcineurin

Holger Husi, Marcel A. Luyten, Mauro G.M. Zurini

Research output: Journal PublicationArticlepeer-review

50 Citations (Scopus)

Abstract

The interaction of the immunosuppressive complexes cyclosporin A- cyclophilin A and FK506 binding protein-FK506 with the Ca2+- and calmodulin-dependent protein phosphatase calcineurin has been investigated by means of photoaffinity labeling and chemical cross-linking. Photolabeling of purified bovine brain calcineurin with the affinity label [O-[4-[4-(1-diazo- 2,2,2-trifluoroethy)benzoyl]aminobutanoyl]-D-serine8]cyclosporin in the presence of cyclophilin A results, in addition to the labeling of cyclophilin itself, in the transfer of some of the chemical probe to both the catalytic subunit A and the regulatory subunit B of calcineurin. Chemical cross- linking studies with disuccinimidyl suberate in the presence of either cyclophilin A, B, or C in complex with cyclosporin A or FK506 binding protein-FK506 result on the other hand in the apparently exclusive and strictly immunosuppressant-dependent formation of covalent immunophilin- calcineurin B subunit products. Cross-linking of immunophilins to calcineurin B subunit requires the presence of subunit A. In the present study, using a set of recombinant maltose-binding protein fusion products representing different stretches of the catalytic subunit A, we were able to map the minimal calcineurin A sequence necessary for immunophilin-ligand-calcineurin B interaction to occur.

Original languageEnglish
Pages (from-to)14199-14204
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number19
Publication statusPublished - 13 May 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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