title: The ability of the immunophilin FKBP59-HBI to interact with the 90-kDa heat shock protein is encoded by its tetratricopeptide repeat domain.
abstract: A protein of apparent molecular mass of approximately 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 immunophilin 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 immunosuppressants FK506 and rapamycin. Examination of the behavior of several mutants led us to conclude that the tetratricopeptide motifs localized in the C-terminal part of FKBP59-HBI are necessary for hsp90 binding.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (U33), Bicêtre, France.
authors.forename: C
authors.initials: C
authors.lastname: Radanyi
authors.forename: B
authors.initials: B
authors.lastname: Chambraud
authors.forename: E E
authors.initials: EE
authors.lastname: Baulieu
mesh_terms: D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002474:Cell-Free System; D004252:DNA Mutational Analysis; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D011090:Polyenes / Q000494:pharmacology; D011485:Protein Binding; D011817:Rabbits; D020123:Sirolimus; D013329:Structure-Activity Relationship; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins
chemical_list: D002352:Carrier Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011090:Polyenes; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus; D016559:Tacrolimus