MOLECULAR-CLONING OF HUMAN FKBP51 AND COMPARISONS OF IMMUNOPHILIN INTERACTIONS WITH HSP90 AND PROGESTERONE-RECEPTOR

A cDNA for human FKBP51 has been cloned and sequenced, and protein pro ducts have been expressed in both in vitro and bacterial systems. The deduced amino acid sequence for human FKBP51 is 90% identical to seque nces of recently described murine proteins and is 55% identical to the sequence of human FKBP52. Human FKBP51 mRNA is expressed in a wide ra nge of tissues, and the protein has peptidylprolyl isomerase activity that is inhibited by FK506 but not cyclosporine. FKBP51 is the same as a previously described progesterone receptor-associated immunophilin that, similar to FKBP52 and cyclophilin 40, is an Hsp90-binding protei n and appears in functionally mature steroid receptor complexes along with Hsp90 and p23. Each of the three receptor-associated immunophilin s displays interactions with progesterone receptor that are more dynam ic than Hsp90-receptor interactions. Whereas FKBP52 and FKBP51 compete about equally well for binding to Hsp90 in a purified system, FKBP51 accumulates preferentially in progesterone receptor complexes assemble d in a cell-free system. This observation provides a precedent for dif ferential interactions between Hsp90-associated immunophilins and targ et proteins such as steroid receptors.