THE ABILITY OF THE IMMUNOPHILIN FKBPB9-HBI TO INTERACT WITH THE 90-KDA HEAT-SHOCK PROTEIN IS ENCODED BY ITS TETRATRICOPEPTIDE REPEAT DOMAIN

A protein of apparent molecular mass of approximate to 59 kDa of the FK506-binding protein class (FKBP59) has been found associated with the heat shock protein hsp90 included in nontransformed steroid receptor complexes and termed FKBP59-HBI (HBI for Heat shock protein 90 Binding Immunophilin). Further data analysis has revealed that this immulnophilin also belongs to the tetratricopeptide repeat family of proteins. In this work, we describe the hsp90-binding domain of FKBP59-HBI. Density gradient centrifugation, gel filtration, and immunoadsorption analyses failed to demonstrate a stable association between FKBP59-HBI and hsp90 in the rabbit reticulocyte lysate. Using a gel-retardation assay, we provide evidence for a specific ATP-independent interaction between highly purified wild-type rabbit FKBP59-HBI and human hsp90 beta. This interaction was not affected by the inmunosuppressants FK506 and rapamycin. Examination of the behavior of several mutants led us to conclude that the tetratricopeptide moths localized in the C-terminal part of FKBP59-HBI are necessary for hsp90 binding.