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.
^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. S2CID 26048417.
^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. PMC2270415. PMID 15845546.
^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.
^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. ISBN9780120342235. ISSN 0065-3233. PMID 4882249.
^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. ISBN978-3-540-40136-0. ISSN 0303-4240. PMID 12698322.
^Prakash, Ajit; Shin, Joon; Rajan, Sreekanth; Yoon, Ho Sup (2016-04-07). "Structural basis of nucleic acid recognition by FK506-binding protein 25 (FKBP25), a nuclear immunophilin". Nucleic Acids Research. 44 (6): 2909–2925. doi:10.1093/nar/gkw001. ISSN 0305-1048. PMC4824100. PMID 26762975.
^(PDF). Archived from the original (PDF) on 2021-02-28.
^Snyder, Solomon; Sabatini, David (January 1998). (PDF). Trends in Pharmacological Sciences. 19 (1): 21–26. doi:10.1016/s0165-6147(97)01146-2. PMID 9509898. Archived from the original (PDF) on 2021-02-28.
March 14, 2024
immunophilins, this, article, needs, additional, citations, verification, please, help, improve, this, article, adding, citations, reliable, sources, unsourced, material, challenged, removed, find, sources, news, newspapers, books, scholar, jstor, 2017, learn,. This article needs additional citations for verification Please help improve this article by adding citations to reliable sources Unsourced material may be challenged and removed Find sources Immunophilins news newspapers books scholar JSTOR May 2017 Learn how and when to remove this template message 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 editFKBP12 FKBP 3 FKBP25 6 FKBP4 FKBP52 FKBP5 FKBP51 References edit 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 S2CID 26048417 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 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 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 Fischer G Aumuller 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 Prakash Ajit Shin Joon Rajan Sreekanth Yoon Ho Sup 2016 04 07 Structural basis of nucleic acid recognition by FK506 binding protein 25 FKBP25 a nuclear immunophilin Nucleic Acids Research 44 6 2909 2925 doi 10 1093 nar gkw001 ISSN 0305 1048 PMC 4824100 PMID 26762975 External links edit 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 2 Portal nbsp Biology Neural actions of immunophilin ligands PDF Archived from the original PDF on 2021 02 28 Snyder Solomon Sabatini David January 1998 Neural actions of immunophilin ligands PDF Trends in Pharmacological Sciences 19 1 21 26 doi 10 1016 s0165 6147 97 01146 2 PMID 9509898 Archived from the original PDF on 2021 02 28 Retrieved from https en wikipedia org w index php title Immunophilins amp oldid 1183258693, wikipedia, wiki, book, books, library,
