Immunophilins: structure—function relationship and possible role in microbial pathogenicity

  title={Immunophilins: structure—function relationship and possible role in microbial pathogenicity},
  author={J{\"o}rg H Hacker and Gunter Fischer},
  journal={Molecular Microbiology},
Immunophilins are housekeeping proteins present in a wide variety of organisms. Members of two protein superfamilies, cyclophilins (Cyps) and FK506‐binding proteins (FKBPs) belong to this class of immunophilins. Despite the fact that the amino acid sequences of Cyp and FKBPs do not exhibit noticeable homology to each other, proteins of both classes are able to ligate immunosuppressive peptide derivatives. Cyps form complexes with the cyclic undecapeptide cyclosporin A and FKBPs are able to bind… 

Characterization of Thylakoid Immunophilins in Arabidopsis

The hypothesis that chloroplast immunophilins have distinct and overlapping functions is supported as they serve as critical regulators in photosynthesis-related processes including the assembly of photosynthetic complexes and adaptation to various light intensities in the natural environment.

Structural and Functional Characterization of a Novel Family of Cyclophilins, the AquaCyps

A novel family of cyclophilins, termed AquaCyps, is identified, which specifically occurs in marine Alphaproteobacteria, but not in related terrestric species, and contains large extensions and insertions.

Mutational analysis of slyD, an Escherichia coli gene encoding a protein of the FKBP immunophilin family

Among the FKBP genes found in organisms across the evolutionary spectrum, slyD is unique in having three distinct drug‐independent phenotypes, which causes significant growth rate defects in Escherichia coli B and C backgrounds.

Escherichia coli and other species of the enterobacteriaceae encode a protein similar to the family of Mip-like FK506-binding proteins

A newly identified gene in Escherichia coli, fkpA, encodes a protein with extensive similarity to the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Chlamydia

Molecular cloning of a Coxiella burnetii gene encoding a macrophage infectivity potentiator (Mip) analogue.

Results demonstrate that C. burnetii encodes a Mip analogue (CbMip), and in view of the role of Mip/Mip-like proteins in the pathogenesis of Legionella and Chlamydia, CbMips may be a C. burningetii virulence factor.

Influence of site specifically altered Mip proteins on intracellular survival of Legionella pneumophila in eukaryotic cells

No differences in intracellular survival were observed between the wild-type isolates and the Legionella strains exhibiting strongly reduced PPIase activity, indicating that the enzymatic activity of Mip does not contribute to intrACEllular survival of L. pneumophila.

A novel FK506- and rapamycin-binding protein (FPR3 gene product) in the yeast Saccharomyces cerevisiae is a proline rotamase localized to the nucleolus

The gene (FPR3) encoding a novel type of peptidylpropyl-cis-trans- isomerase (PPIase) was isolated during a search for previously unidentified nuclear proteins in Saccharomyces cerevisiae and demonstrated that Fpr3 is located exclusively in the nucleolus.



Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl‐prolyl cis‐trans isomerases

The results lead to the suggestion that several genes encoding isozymic forms of the FKBPs and possibly also of the cyclophilins existed in prokaryotes before the emergence of eukaryotes on earth and that representatives of these genes were transmitted to both kingdoms to give rise to current subfamilies of these proteins.

Solution structure of the major binding protein for the immunosuppressant FK506

The solution conformation of FKBP, as generated by NMR, distance geometry and molecular dynamics methods, suggests a possible site of interaction with FK506.

Neisseria meningitidis encodes an FK506-inhibitable rotamase.

  • B. SampsonE. Gotschlich
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1992
Using the polymerase chain reaction, a homolog of an FK506-binding protein from Neisseria meningitidis is cloned and sequenced and expressed the gene product as a fusion protein with maltose-bindingprotein, which had rotamase activity comparable to that of human Fk506- binding protein.

Streptomycetes possess peptidyl‐prolyl cis‐trans isomerases that strongly resemble cyclophilins from eukaryotic organisms

A functionally active 17.5 kDa peptidyl‐prolyl cis‐trans isomerase was purified to homogeneity from Streptomyces chrysomallus, a Gram‐positive filamentous bacterium, and revealed inhibition and binding characteristics, against the immunsuppressive drug cyclosporin A.

X-ray structure of a decameric cyclophilin-cyclosporin crystal complex

The crystal structure of a decameric CypA–CsA complex is described, providing an unambiguous picture of the detailed interactions between a peptide drug and its receptor, and broadly confirms the results of previous NMR, X-ray and modelling studies, but provides further important structural details which will be of use in the design of drugs that are analogues of CsA.

A yeast cyclophilin gene essential for lactate metabolism at high temperature.

A conditional lethal phenotype for a cyclophilin mutation is demonstrated and a system for genetic and biochemical analysis of cyclophILin function is presented and presented.

FKBl encodes a nonessential FK 506-binding protein in Saccharomyces cerevisiae and contains regions suggesting homology to the cyclophilins

A search of translated nucleic acid data bases revealed bacterial FKBP homologs in Neisseria meningiditis and Pseudomonas aeruginosa and revealed a region of similarity that is speculated to be a homologous domain related to the functional similarities of the two proteins.

Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins

The results indicate that this enzyme is probably identical to cyclophilin, a recently discovered mammalian protein which binds tightly to cyclosporin A (CsA), which is thought to be linked to the immunosuppressive action of CsA.