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 CD59gene.[5] It is an LU domain and belongs to the LY6/uPAR/alpha-neurotoxinprotein family.[6]
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.[7] When complement activation leads to deposition of C5b678 on host cells, CD59 can prevent C9 from polymerizing and forming the complement membrane attack complex.[8] It may also signal the cell to perform active measures such as endocytosis of the CD59-C9 complex.[6] 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.[9]
Mutations affecting GPI that reduce expression of CD59 and decay-accelerating factoronred blood cells result in paroxysmal nocturnal hemoglobinuria.[10] 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.[11]
Viruses such as HIV, human cytomegalovirus and vaccinia incorporate host cell CD59 into their own viral envelope to prevent lysis by complement.[12] 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.[13]
^ abMaio M, Brasoveanu LI, Coral S, Sigalotti L, Lamaj E, Gasparollo A, Visintin A, Altomonte M, Fonsatti E (Aug 1998). "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. doi:10.3892/ijo.13.2.305. PMID9664126.
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. PMID1376264. S2CID25836496.
Motoyama N, Okada N, Yamashina M, Okada H (1992). "Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene". Eur. J. Immunol. 22 (10): 2669–2673. doi:10.1002/eji.1830221029. PMID1382994. S2CID23829471.
Tone M, Walsh LA, Waldmann H (1992). "Gene structure of human CD59 and demonstration that discrete mRNAs are generated by alternative polyadenylation". J. Mol. Biol. 227 (3): 971–976. doi:10.1016/0022-2836(92)90239-G. PMID1383553.
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. PMID1689664. S2CID23636682.
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. PMID1692709.
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. PMID2606909.
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. PMID7505007.
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. PMID7512825.
1cdq: STRUCTURE OF A SOLUBLE, GLYCOSYLATED FORM OF THE HUMAN COMPLEMENT REGULATORY PROTEIN CD59
1cdr: STRUCTURE OF A SOLUBLE, GLYCOSYLATED FORM OF THE HUMAN COMPLEMENT REGULATORY PROTEIN CD59
1cds: STRUCTURE OF A SOLUBLE, GLYCOSYLATED FORM OF THE HUMAN COMPLEMENT REGULATORY PROTEIN CD59
1erg: THREE-DIMENSIONAL SOLUTION STRUCTURE OF THE EXTRACELLULAR REGION OF THE COMPLEMENT REGULATORY PROTEIN, CD59, A NEW CELL SURFACE PROTEIN DOMAIN RELATED TO NEUROTOXINS
1erh: THREE-DIMENSIONAL SOLUTION STRUCTURE OF THE EXTRACELLULAR REGION OF THE COMPLEMENT REGULATORY PROTEIN, CD59, A NEW CELL SURFACE PROTEIN DOMAIN RELATED TO NEUROTOXINS
