Jump to content

Immunophilins: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
m +wls
m +wl
Line 2: Line 2:
In [[molecular biology]], '''immunophilins''' are endogenous cytosolic [[peptidyl-prolyl isomerase]]s (PPI) that catalyze the interconversion between the [[Cis–trans isomerism|cis and trans isomers]] of peptide bonds containing the amino acid proline (Pro). They are [[chaperone molecule]]s 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 [[cyclophilin]]s (CyPs)" and "FK506-binding proteins ([[FKBP]]s)".<ref>{{Cite journal|last=Barik|first=S.|date=December 2006|title=Immunophilins: for the love of proteins|journal=Cellular and Molecular Life Sciences|volume=63|issue=24|pages=2889–2900|doi=10.1007/s00018-006-6215-3|issn=1420-682X|pmid=17075696}}</ref> 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).<ref>{{Cite journal|last=Adams|first=Brian|last2=Musiyenko|first2=Alla|last3=Kumar|first3=Rajinder|last4=Barik|first4=Sailen|date=2005-07-01|title=A novel class of dual-family immunophilins|journal=The Journal of Biological Chemistry|volume=280|issue=26|pages=24308–24314|doi=10.1074/jbc.M500990200|issn=0021-9258|pmc=2270415|pmid=15845546}}</ref>
In [[molecular biology]], '''immunophilins''' are endogenous cytosolic [[peptidyl-prolyl isomerase]]s (PPI) that catalyze the interconversion between the [[Cis–trans isomerism|cis and trans isomers]] of peptide bonds containing the amino acid proline (Pro). They are [[chaperone molecule]]s 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 [[cyclophilin]]s (CyPs)" and "FK506-binding proteins ([[FKBP]]s)".<ref>{{Cite journal|last=Barik|first=S.|date=December 2006|title=Immunophilins: for the love of proteins|journal=Cellular and Molecular Life Sciences|volume=63|issue=24|pages=2889–2900|doi=10.1007/s00018-006-6215-3|issn=1420-682X|pmid=17075696}}</ref> 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).<ref>{{Cite journal|last=Adams|first=Brian|last2=Musiyenko|first2=Alla|last3=Kumar|first3=Rajinder|last4=Barik|first4=Sailen|date=2005-07-01|title=A novel class of dual-family immunophilins|journal=The Journal of Biological Chemistry|volume=280|issue=26|pages=24308–24314|doi=10.1074/jbc.M500990200|issn=0021-9258|pmc=2270415|pmid=15845546}}</ref>


Immunophilins act as receptors for [[immunosuppressive drug]]s such as [[sirolimus]] (rapamycin), [[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.<ref>{{Cite journal|last=Ho|first=S.|last2=Clipstone|first2=N.|last3=Timmermann|first3=L.|last4=Northrop|first4=J.|last5=Graef|first5=I.|last6=Fiorentino|first6=D.|last7=Nourse|first7=J.|last8=Crabtree|first8=G. R.|date=September 1996|title=The mechanism of action of cyclosporin A and FK506|journal=Clinical Immunology and Immunopathology|volume=80|issue=3 Pt 2|pages=S40–45|issn=0090-1229|pmid=8811062|doi=10.1006/clin.1996.0140}}</ref> CsA and FK506 thus affect the calcium-dependent step of T cell response which prevents release of [[Interleukin 2|interleukin-2]]. Immunophilins also form protein complex with [[ryanodine]] and [[Inositol trisphosphate|inositol triphosphate]] (IP3) which impacts the release of calcium.
Immunophilins act as receptors for [[immunosuppressive drug]]s such as [[sirolimus]] (rapamycin), [[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.<ref>{{Cite journal|last=Ho|first=S.|last2=Clipstone|first2=N.|last3=Timmermann|first3=L.|last4=Northrop|first4=J.|last5=Graef|first5=I.|last6=Fiorentino|first6=D.|last7=Nourse|first7=J.|last8=Crabtree|first8=G. R.|date=September 1996|title=The mechanism of action of cyclosporin A and FK506|journal=Clinical Immunology and Immunopathology|volume=80|issue=3 Pt 2|pages=S40–45|issn=0090-1229|pmid=8811062|doi=10.1006/clin.1996.0140}}</ref> CsA and FK506 thus affect the calcium-dependent step of [[T cell]] response which prevents release of [[Interleukin 2|interleukin-2]]. Immunophilins also form protein complex with [[ryanodine]] and [[Inositol trisphosphate|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 bond]]s within proteins exist in trans (planar) conformation because of the partial double-bond nature of the peptide bond,<ref>{{Cite journal|last=Ramachandran|first=G. N.|last2=Sasisekharan|first2=V.|date=1968|title=Conformation of polypeptides and proteins|journal=Advances in Protein Chemistry|volume=23|pages=283–438|issn=0065-3233|pmid=4882249|doi=10.1016/S0065-3233(08)60402-7|isbn=9780120342235}}</ref> 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.<ref>{{Cite journal|last=Fischer|first=G.|last2=Aumüller|first2=T.|date=2003|title=Regulation of peptide bond cis/trans isomerization by enzyme catalysis and its implication in physiological processes|journal=Reviews of Physiology, Biochemistry and Pharmacology|volume=148|pages=105–150|doi=10.1007/s10254-003-0011-3|issn=0303-4240|pmid=12698322|isbn=978-3-540-40136-0}}</ref> Immunophilins, with their prolyl isomerase activity, thus function as protein-folding chaperones.
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 bond]]s within proteins exist in trans (planar) conformation because of the partial double-bond nature of the peptide bond,<ref>{{Cite journal|last=Ramachandran|first=G. N.|last2=Sasisekharan|first2=V.|date=1968|title=Conformation of polypeptides and proteins|journal=Advances in Protein Chemistry|volume=23|pages=283–438|issn=0065-3233|pmid=4882249|doi=10.1016/S0065-3233(08)60402-7|isbn=9780120342235}}</ref> 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.<ref>{{Cite journal|last=Fischer|first=G.|last2=Aumüller|first2=T.|date=2003|title=Regulation of peptide bond cis/trans isomerization by enzyme catalysis and its implication in physiological processes|journal=Reviews of Physiology, Biochemistry and Pharmacology|volume=148|pages=105–150|doi=10.1007/s10254-003-0011-3|issn=0303-4240|pmid=12698322|isbn=978-3-540-40136-0}}</ref> Immunophilins, with their prolyl isomerase activity, thus function as protein-folding chaperones.

Revision as of 23:59, 2 June 2021

In molecular biology, immunophilins are endogenous cytosolic peptidyl-prolyl isomerases (PPI) that catalyze the interconversion between the cis and trans isomers of peptide bonds containing the amino acid proline (Pro). They are 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 immunosuppressive drugs such as sirolimus (rapamycin), 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. ^ Barik, S. (December 2006). "Immunophilins: for the love of proteins". Cellular and Molecular Life Sciences. 63 (24): 2889–2900. doi:10.1007/s00018-006-6215-3. ISSN 1420-682X. PMID 17075696.
  2. ^ Adams, Brian; Musiyenko, Alla; Kumar, Rajinder; Barik, Sailen (2005-07-01). "A novel class of dual-family immunophilins". The Journal of Biological Chemistry. 280 (26): 24308–24314. doi:10.1074/jbc.M500990200. ISSN 0021-9258. PMC 2270415. PMID 15845546.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ Ho, S.; Clipstone, N.; Timmermann, L.; Northrop, J.; Graef, I.; Fiorentino, D.; Nourse, J.; Crabtree, G. R. (September 1996). "The mechanism of action of cyclosporin A and FK506". Clinical Immunology and Immunopathology. 80 (3 Pt 2): S40–45. doi:10.1006/clin.1996.0140. ISSN 0090-1229. PMID 8811062.
  4. ^ Ramachandran, G. N.; Sasisekharan, V. (1968). "Conformation of polypeptides and proteins". Advances in Protein Chemistry. 23: 283–438. doi:10.1016/S0065-3233(08)60402-7. ISBN 9780120342235. ISSN 0065-3233. PMID 4882249.
  5. ^ Fischer, G.; Aumüller, T. (2003). "Regulation of peptide bond cis/trans isomerization by enzyme catalysis and its implication in physiological processes". Reviews of Physiology, Biochemistry and Pharmacology. 148: 105–150. doi:10.1007/s10254-003-0011-3. ISBN 978-3-540-40136-0. ISSN 0303-4240. PMID 12698322.
  • [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


    Stub icon

    This enzyme-related article is a stub. You can help Wikipedia by expanding it.

    Stub icon

    This immunology article is a stub. You can help Wikipedia by expanding it.

    1. ^ "Neural actions of immunophilin ligands" (PDF).
    2. ^ Snyder, Solomon; Sabatini, David (January 1998). "Neural actions of immunophilin ligands" (PDF).
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Immunophilins&oldid=1026555904"