CD59 glycoprotein, also known asMAC-inhibitory protein (MAC-IP),membrane inhibitor of reactive lysis (MIRL), orprotectin, is aprotein that in humans is encoded by theCD59gene.[5] It is anLU domain and belongs to theLY6/uPAR/alpha-neurotoxinprotein family.[6]
CD59 attaches to host cells via aglycophosphatidylinositol (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] Whencomplement activation leads to deposition of C5b678 on host cells, CD59 can preventC9 from polymerizing and forming thecomplement membrane attack complex.[8] It may alsosignal the cell to perform active measures such asendocytosis 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 andAlzheimer's disease.[9]
Mutations affecting GPI that reduce expression of CD59 anddecay-accelerating factor onred blood cells result inparoxysmal 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 asHIV, humancytomegalovirus andvaccinia incorporate host cell CD59 into their ownviral 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 inMCF-7 cells.[13]
PDB gallery | |
|---|---|
|
