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 products have been expressed in both in vitro and bacterial systems. The deduced amino acid sequence for human FKBP51 is 90% identical to sequences of recently described murine proteins and is 55% identical to the sequence of human FKBP52. Human FKBP51 mRNA is expressed in a wide range 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 protein and appears in functionally mature steroid receptor complexes along with Hsp90 and p23. Each of the three receptor-associated immunophilins displays interactions with progesterone receptor that are more dynamic 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 assembled in a cell-free system. This observation provides a precedent for differential interactions between Hsp90-associated immunophilins and target proteins such as steroid receptors.
Nair
S C
SC
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Rimerman
R A
RA
Toran
E J
EJ
Chen
S
S
Prapapanich
V
V
Butts
R N
RN
Smith
D F
DF
D000591:Amino Acid Isomerases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002474:Cell-Free System; D002645:Chickens; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D019696:Peptidylprolyl Isomerase; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D011980:Receptors, Progesterone / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D011993:Recombinant Fusion Proteins; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus