9 research outputs found
Principles for the design of advanced flight director systems based on the theory of manual control displays
Design and development of flight director systems based on theory of manual control display
Pilot describing function measurements in a multiloop task
Pilot describing function measurements in multiloop control system tracking tas
Small perturbation dynamics of the neuromuscular system in tracking tasks
Small perturbation dynamics of neuromuscular system in tracking task
Explaining the absence of the lay voice in sexual health through sociological theories of healthcare
FKBP (FK506 Binding Protein)
In the 70s, after a decade from the purification of cyclosporine, a selective immunosuppressant
agent and potent tool in transplantation medicine, a novel molecule was purified from bacteria
Streptomyces tsukubaensis. This molecule, called FK506, showed the same selective
immunosuppressant action as cyclosporine but was 10 to 100 fold more potent.
In an attempt to clarify the molecular mechanism through which the new drug exerted such a
selective effect on T-cells activation, two laboratories identified the cytosolic receptor for FK506.
This so-called FK506 binding protein (FKBP) was purified from bovine thymus, human spleen, and
Jurkat T-cell line. The isolated FKBP had an approximate molecular mass of 14 kDa and showed
an isomerase activity similar to the recently purified cyclosporine-binding protein, cyclophilin, but, it
was inhibited by FK506 and rapamycin but not cyclosporine. The
subsequent cloning of FKBP gene revealed that FKBP and cyclophilin had dissimilar sequences in
spite of their common enzymatic activity. The identified FKBP gene encoded for a protein of 108
aminoacids with a relative molecular mass of 11,819. For this reason, the progenitor of this
nascent class of proteins was later known as FKBP12.
The subsequent studies showed that FKBP12 was just a member of a ubiquitous and evolutionarily
conserved sub-family of proteins which differ from each other in their molecular weight and
structure. All FKBPs share a highly conserved domain, termed “FK-12 like domain”, capable of
binding to FK506 and exerting isomerase properties, i.e. interconversion from cis-to-trans and
trans-to-cis of peptide bonds involving proline, on protein substrates.
A schematic historical background of the 17 FKBPs so far identified is shown. A general
overview of FKBP structure, function and eventually associated disease is given in this
monograph, with the order of proteins following the chronology of discovery