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.
CD59 is a GPI-anchored protein crucial for immune regulation by inhibiting MAC formation and protecting human cells from complement-driven destruction.
It belongs to a neurotoxin protein family.
CD59 attaches to host cells via a glycophosphatidylinositol (GPI) anchor.
When complement activation leads to deposition of C5b678 on host cells, CD59 can prevent C9 from polymerizing and forming the complement membrane attack complex.
It may also signal the cell to perform endocytosis of the CD59-C9 complex.
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 cell membrane, and without this severe symptoms and diseases can occur such as neuron degeneration and Alzheimer’s disease.
Mutations affecting GPI that reduce expression of CD59 and decay-accelerating factor on red blood cells result in paroxysmal nocturnal hemoglobinuria.
Genetic defects or reduced expression of CD59 (as seen in paroxysmal nocturnal hemoglobinuria) can result in increased susceptibility to cell lysis and related diseases.
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 (glycophosphatidylinositol)GPI-CD59 complex binding.
Viruses such as HIV, human cytomegalovirus and vaccinia incorporate host cell CD59 into their own viral envelope to prevent lysis by complement.
Once CD59 had been targeted by immunotherapy there is an upregulation in fas and caspase-3, creating an increase in apoptosis and tumor growth suppression in MCF-7 cells.
CD59 is a glycoprotein anchored to the cell surface by a glycosylphosphatidylinositol (GPI) anchor that acts as a key regulator of the complement system, specifically inhibiting the formation of the membrane attack complex (MAC) to protect human cells from complement-mediated lysis.
It is highly expressed on blood cells, endothelial cells, and various nonvascular cell types.
CD59 binds to complement proteins C8 and C9 during MAC assembly, blocking C9 polymerization and thus preventing pore formation in the cell membrane.
This inhibition is essential for protecting host tissue from inadvertent damage during immune responses.
Certain viruses and pathogens can hijack or mimic CD59 to evade immune destruction.
Has a role in promoting tumor cell survival by preventing complement-mediated cell death.