Organization and function of the FKBP52 and FKBP51 genes

Abstract

Best established as components of steroid hormone receptor complexes, it is now clear that the large molecular weight immunophilins, FKBP52 and FKBP51, play important regulatory roles elsewhere in the cell. This review outlines what is known about the organization of the genes, FKBP4 and FKBP5 respectively, encoding these proteins and describes their diverse actions in the nervous system, reproduction, and cancer. The organization of FKBP4 and FKBP5 is very similar among the chordates, and gene expression is influenced by both genetic and epigenetic mechanisms. Recent studies identifying roles of FKBP52 and FKBP51 in regulation of the microtubule-associated protein tau and microtubule assembly are discussed, as is their interaction with and influence on the transient receptor potential canonical subfamily of ion channel proteins.

Plant immunophilins: a review of their structure-function relationship

“…Similarly, AtFKBP65 is a heat stress protein but fkbp65 mutant plants are resistant to heat stress and small heat shock proteins are highly expressed, contrary to what is observed in fkbp62 mutants, indicating antagonistic functions [36]. Equally, the mammalian FKBP51/FKBP52 orthologs of AtFKBP62/AtFKBP65 have also been shown to have antagonist functions in steroid receptor-mediated signaling [112,113]. On a similar note, transgenic wheat overexpressing TaFKBP73 and TaFKBP77 revealed different morphological abnormalities, indicating different functional attributes for the two isoforms in plant development [114].…”

“…The major contribution to this significant difference is coming from the redox active C-terminal loop [90]. The catalytic domains are significantly shifted and twisted compared with the oxidized structure and this results in differences of up to 10 Å. Superimposition of only the catalytic domains of the reduced structure and the corresponding parts of the oxidized structure gives an RMSD of 1.48 Å for 17 Cα atoms (residues [100][101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116]. Reduction of the disulfide bond leads to an increase in the distance between the sulfur atoms of the two cysteines: the observed S-S distance in AtFKBP13-S2 Cys5-Cys17 and Cys106-Cys111 are 2.04 ± 0.01 and 2.01 ± 0.01 Å, respectively as expected for a disulfide bond, whereas the corresponding distance is 5.18 Å and 2.81 Å for AtFKBP13-(SH)2 [90].…”

NF-κB Transcriptional Activity Is Modulated by FK506-binding Proteins FKBP51 and FKBP52

“…Both FKBPs are also regulators of the ligand-dependent transcriptional activity for those receptors (18 -20) and other members of the family such as PR (21,22), AR (23,24), and to a minor degree, estrogen receptor ␣ (22,25). These Hsp90 binding immunophilins are highly homologous and share 60% homology and 75% similarity (26). They are structurally characterized by the presence of two key sequences: the TPR domain, through which they bind to Hsp90, and the peptidyl-prolyl isomerase (PPIase) domain (27), where the macrolide FK506 and also the dynein⅐dynactin motor complex bind.…”

Selective inhibitors of the FK506-binding protein 51 by induced fit

“…F KBP51 and FKBP52 are peptidyl-prolyl cis/trans-isomerases (PPIases) that participate as cochaperones in the Hsp90 protein folding machinery [1][2][3][4] . Like most members of the immuno philin protein family, they tightly bind the immunosuppressive drugs FK506 and rapamycin 5 .…”