Immunophilins

Source: Wikipedia, the free encyclopedia.

In

chaperone molecules that generally assist in the proper folding of diverse "client" proteins. Immunophilins are traditionally classified into two families that differ in sequence and biochemical characteristics. These two families are: "cyclosporin-binding cyclophilins (CyPs)" and "FK506-binding proteins (FKBPs)".[1] In 2005, a group of dual-family immunophilins (DFI) has been discovered, mostly in unicellular organisms; these DFIs are natural chimera of CyP and FKBPs, fused in either order (CyP-FKBP or FKBP-CyP).[2]

Immunophilins act as receptors for

cyclosporin (such as CsA) and tacrolimus (FK506), which inhibit the prolyl isomerase activity of the immunophilins. The drug-immunophilin complexes (CsA-CyP and FK506-FKBP) bind to calcineurin, which inhibits the phosphatase activity of calcineurin and engenders the immunosuppressive effects.[3] CsA and FK506 thus affect the calcium-dependent step of T cell response which prevents release of interleukin-2. Immunophilins also form protein complex with ryanodine and inositol triphosphate
(IP3) which impacts the release of calcium.

FK506 binds with high affinity to other smaller proteins, such as FKBP-12. FKBP-12 and cyclophilins both share common peptide-prolyl isomerase activity. While the majority of the Peptide bonds within proteins exist in trans (planar) conformation because of the partial double-bond nature of the peptide bond,[4] a small fraction occurs in cis. Unlike regular peptide bonds, the X-Pro peptide bond does not adopt the intended trans conformation spontaneously, thus, cis-trans isomerization can be the rate-limiting (slowest) step in the process of protein folding.[5] Immunophilins, with their prolyl isomerase activity, thus function as protein-folding chaperones.

See also

References

  1. S2CID 26048417
    .
  2. PMID 15845546
    .
  3. PMID 8811062
    .
  4. PMID 4882249
    .
  5. PMID 12698322
    .
  6. PMID 26762975
    .

External links

  • [1]Immunophilins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  • "Plant immunophilins and signal transduction" at berkeley.edu
  • http://www.jbc.org/content/280/26/24308.full
    1. ^ "Neural actions of immunophilin ligands" (PDF). Archived from the original (PDF) on 2021-02-28.
    2. PMID 9509898. Archived from the original
      (PDF) on 2021-02-28.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Immunophilins&oldid=1183258693"