Biology:CD59
 Generic protein structure example |
CD59 glycoprotein, also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is a protein that in humans is encoded by the CD59 gene.[1] It is an LU domain and belongs to the LY6/uPAR/alpha-neurotoxin protein family.[2]
CD59 attaches to host cells via a glycophosphatidylinositol (GPI) anchor. Cholesterol-containing microdomains aid in CD59 activity by stimulating a “pinch point” in the lipid membrane during MAC assembly to prevent pore-formation and inhibit lysing.[3] When complement activation leads to deposition of C5b678 on host cells, CD59 can prevent C9 from polymerizing and forming the complement membrane attack complex.[4] It may also signal the cell to perform active measures such as endocytosis of the CD59-C9 complex.[2]Endocytosis of this complex leads to the destruction of the ion channel formation that this complex provides to the MAC. These ion channels are used for transfer of different ions to maintain the correct concentration of minerals inside and outside of the membrane, and without this correct maintenance, severe symptoms and diseases can occur such as neuron degeneration and Alzheimer’s Disease.[5]
Mutations affecting GPI that reduce expression of CD59 and decay-accelerating factor on red blood cells result in paroxysmal nocturnal hemoglobinuria.[6]GPI mutation and consequent reduction in CD59 expression results from a cysteine to tyrosine missense mutation, which prevents disulfide bridge formation, ultimately disrupting tertiary protein structure and preventing proper GPI-CD59 complex binding.[7]
Viruses such as HIV, human cytomegalovirus and vaccinia incorporate host cell CD59 into their own viral envelope to prevent lysis by complement.[8]Additionally, CD59 has been investigated as a target for immunotherapy when treating certain cancers such as breast cancer. Researchers have found that once CD59 had been targeted, there is an upregulation in fas and caspase-3, creating an increase in apoptosis and tumor growth suppression in MCF-7 cells.[9]
References
- ↑ "Entrez Gene: CD59 molecule, complement regulatory protein". https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=966&rn=1.
- ↑ 2.0 2.1 "Structure, distribution, and functional role of protectin (CD59) in complement-susceptibility and in immunotherapy of human malignancies (Review)". International Journal of Oncology 13 (2): 305–18. Aug 1998. doi:10.3892/ijo.13.2.305. PMID 9664126.
- ↑ Couves, Emma C.; Gardner, Scott; Voisin, Tomas B.; Bickel, Jasmine K.; Stansfeld, Phillip J.; Tate, Edward W.; Bubeck, Doryen (2023-02-16). "Structural basis for membrane attack complex inhibition by CD59" (in en). Nature Communications 14 (1): 890. doi:10.1038/s41467-023-36441-z. ISSN 2041-1723. PMID 36797260. Bibcode: 2023NatCo..14..890C.
- ↑ "Defining the CD59-C9 binding interaction". J. Biol. Chem. 281 (37): 27398–27404. September 2006. doi:10.1074/jbc.M603690200. PMID 16844690.
- ↑ Farkas, Imre; Baranyi, Lajos; Ishikawa, Yasushige; Okada, Noriko; Bohata, Csaba; Budai, Denes; Fukuda, Atsuo; Imai, Masaki et al. (2002–2003). "CD59 blocks not only the insertion of C9 into MAC but inhibits ion channel formation by homologous C5b-8 as well as C5b-9". The Journal of Physiology 539 (2): 537–545. doi:10.1113/jphysiol.2001.013381. ISSN 0022-3751. PMID 11882685. PMC 2290142. http://dx.doi.org/10.1113/jphysiol.2001.013381.
- ↑ "Diagnosis and management of paroxysmal nocturnal hemoglobinuria". Blood 106 (12): 3699–709. 2005. doi:10.1182/blood-2005-04-1717. PMID 16051736.
- ↑ Nevo, Yoram; Ben-Zeev, Bruria; Tabib, Adi; Straussberg, Rachel; Anikster, Yair; Shorer, Zamir; Fattal-Valevski, Aviva; Ta-Shma, Asaf et al. (2013-01-03). "CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune-mediated polyneuropathy". Blood 121 (1): 129–135. doi:10.1182/blood-2012-07-441857. ISSN 0006-4971. PMID 23149847.
- ↑ "Cell signals transduced by complement". Mol. Immunol. 41 (6–7): 583–597. July 2004. doi:10.1016/j.molimm.2004.04.007. PMID 15219997.
- ↑ Li, Bing; Chu, Xianming; Gao, Meihua; Xu, Yingjie (2011). "The effects of CD59 gene as a target gene on breast cancer cells" (in en). Cellular Immunology 272 (1): 61–70. doi:10.1016/j.cellimm.2011.09.006. PMID 22000275. https://linkinghub.elsevier.com/retrieve/pii/S0008874911002395.
Further reading
- "Expression and function of membrane attack complex inhibitory proteins on thyroid follicular cells". Immunology 75 (2): 372–7. 1992. PMID 1372592.
- Holmes CH; Simpson KL; Okada H et al. (1992). "Complement regulatory proteins at the feto-maternal interface during human placental development: distribution of CD59 by comparison with membrane cofactor protein (CD46) and decay accelerating factor (CD55)". Eur. J. Immunol. 22 (6): 1579–1585. doi:10.1002/eji.1830220635. PMID 1376264.
- Hahn WC; Menu E; Bothwell AL et al. (1992). "Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59". Science 256 (5065): 1805–1807. doi:10.1126/science.1377404. PMID 1377404. Bibcode: 1992Sci...256.1805H.
- "The human complement regulatory protein CD59 binds to the alpha-chain of C8 and to the "b"domain of C9". J. Biol. Chem. 267 (19): 13675–80. 1992. doi:10.1016/S0021-9258(18)42266-1. PMID 1377690.
- Petranka JG; Fleenor DE; Sykes K et al. (1992). "Structure of the CD59-encoding gene: further evidence of a relationship to murine lymphocyte antigen Ly-6 protein". Proc. Natl. Acad. Sci. U.S.A. 89 (17): 7876–7879. doi:10.1073/pnas.89.17.7876. PMID 1381503. Bibcode: 1992PNAS...89.7876P.
- "Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene". Eur. J. Immunol. 22 (10): 2669–2673. 1992. doi:10.1002/eji.1830221029. PMID 1382994.
- "Characterization of the membrane attack complex inhibitory protein CD59 antigen on human amniotic cells and in amniotic fluid". Immunology 76 (4): 541–7. 1992. PMID 1383132.
- "Gene structure of human CD59 and demonstration that discrete mRNAs are generated by alternative polyadenylation". J. Mol. Biol. 227 (3): 971–976. 1992. doi:10.1016/0022-2836(92)90239-G. PMID 1383553.
- Philbrick WM; Palfree RG; Maher SE et al. (1990). "The CD59 antigen is a structural homologue of murine Ly-6 antigens but lacks interferon inducibility". Eur. J. Immunol. 20 (1): 87–92. doi:10.1002/eji.1830200113. PMID 1689664.
- Sawada R; Ohashi K; Anaguchi H et al. (1990). "Isolation and expression of the full-length cDNA encoding CD59 antigen of human lymphocytes". DNA Cell Biol. 9 (3): 213–220. doi:10.1089/dna.1990.9.213. PMID 1692709.
- Yamashina M; Ueda E; Kinoshita T et al. (1990). "Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria". N. Engl. J. Med. 323 (17): 1184–1189. doi:10.1056/NEJM199010253231707. PMID 1699124.
- "Protection of human amniotic epithelial cells (HAEC) from complement-mediated lysis: expression on the cells of three complement inhibitory membrane proteins". Immunology 71 (3): 308–11. 1991. PMID 1702747.
- "Isolation and characterization of a membrane-attack-complex-inhibiting protein present in human serum and other biological fluids". Biochem. J. 265 (2): 471–7. 1990. doi:10.1042/bj2650471. PMID 2302178.
- Okada H; Nagami Y; Takahashi K et al. (1989). "20 KDa homologous restriction factor of complement resembles T cell activating protein". Biochem. Biophys. Res. Commun. 162 (3): 1553–1559. doi:10.1016/0006-291X(89)90852-8. PMID 2475111.
- Davies A; Simmons DL; Hale G et al. (1989). "CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells". J. Exp. Med. 170 (3): 637–654. doi:10.1084/jem.170.3.637. PMID 2475570.
- Sawada R; Ohashi K; Okano K et al. (1989). "Complementary DNA sequence and deduced peptide sequence for CD59/MEM-43 antigen, the human homologue of murine lymphocyte antigen Ly-6C". Nucleic Acids Res. 17 (16): 6728. doi:10.1093/nar/17.16.6728. PMID 2476718.
- Sugita Y; Tobe T; Oda E et al. (1990). "Molecular cloning and characterization of MACIF, an inhibitor of membrane channel formation of complement". J. Biochem. 106 (4): 555–7. doi:10.1093/oxfordjournals.jbchem.a122893. PMID 2606909.
- Bora NS; Gobleman CL; Atkinson JP et al. (1994). "Differential expression of the complement regulatory proteins in the human eye". Invest. Ophthalmol. Vis. Sci. 34 (13): 3579–84. PMID 7505007.
- Kieffer B; Driscoll PC; Campbell ID et al. (1994). "Three-dimensional solution structure of the extracellular region of the complement regulatory protein CD59, a new cell-surface protein domain related to snake venom neurotoxins". Biochemistry 33 (15): 4471–4482. doi:10.1021/bi00181a006. PMID 7512825.
- Kennedy SP; Rollins SA; Burton WV et al. (1994). "Protection of porcine aortic endothelial cells from complement-mediated cell lysis and activation by recombinant human CD59". Transplantation 57 (10): 1494–501. doi:10.1097/00007890-199405000-00017. PMID 7515200.
External links
- CD59+Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
- Human CD59 genome location and CD59 gene details page in the UCSC Genome Browser.
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