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#CD59

1 public question tagged with this topic.

What type of lipid linkage does CD59 have?

CD59 protectin MIRL MAC-inhibitory protein exemplifies complement regulation through GPI anchoring. Gene located chromosome eleven encodes one hundred twenty eight amino acids including twenty six residue C-terminal GPI signal peptide removed in endoplasmic reticulum. Preassembled GPI precursor synthesized via stepwise addition of N-acetylglucosamine to phosphatidylinositol, deacetylation, addition of three mannose residues via PIG enzymes, and phosphoethanolamine addition is transferred en bloc by GPI transamidase containing PIG-K catalytic subunit forming amide bond between protein and phosphoethanolamine linked to terminal mannose, core glycan containing glucosamine connecting to inositol phospholipid diacylglycerol embedded in outer leaflet. Resulting anchor confers partition into lipid rafts and rapid lateral diffusion to sites of complement activation where CD59 binds C8 alpha and C9 first transmembrane region blocking polymerization of membrane attack complex pore. Bacterial PI-PLC cleavage releases CD59. Paroxysmal nocturnal hemoglobinuria caused by somatic PIGA mutation disrupting GPI synthesis eliminates CD59 and CD55 causing hemolysis detected by flow cytometry FLAER staining.

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Section: GPI-Anchored Proteins – CD59 and Complement Regulation.