CD59 Antibody (Mouse mAb) [M4G24]

CD59 Antibody (Mouse mAb) [M4G24] detects endogenous levels of total CD59 protein.

CD59 is a small, glycosylphosphatidylinositol-anchored membrane glycoprotein that functions as the principal cell-surface inhibitor of the terminal complement pathway, expressed broadly across hematopoietic and non-hematopoietic human cells. The membrane attack complex assembles through the sequential recruitment of complement proteins C5b, C6, C7, C8, and C9, a process in which C8 and C9 each undergo a dramatic conformational transition, unfurling helical bundles within their MACPF domains into membrane-inserting β-hairpins that drive pore formation. CD59 does not bind soluble C8 or C9 but engages both proteins specifically once they are incorporated into the nascent complex, capturing the C5b-8 and C5b-9 assembly intermediates before pore insertion occurs. CD59 binds the pore-forming β-hairpin region of C8, forming an intermolecular β-sheet that physically blocks membrane perforation by C8 itself, while simultaneously deflecting the trajectory of the first incoming C9 β-hairpin as it attempts to insert into the membrane. By rerouting this initial C9 insertion, CD59 restricts the conformational transition required for subsequent C9 monomers to join the growing pore, halting polymerization of the full membrane attack complex rather than blocking any single binding step in isolation. This dual mechanism, direct steric blockade of C8 and indirect disruption of C9 polymerization, allows a single CD59 molecule to arrest membrane attack complex assembly at more than one stage of its stepwise construction. Loss of CD59 from the cell surface, together with the related regulator CD55, results almost universally from somatic mutation in the PIGA gene, which disrupts the first step of glycosylphosphatidylinositol anchor biosynthesis and prevents proper anchoring of both proteins to affected hematopoietic cells. This GPI-anchor deficiency underlies paroxysmal nocturnal hemoglobinuria, in which the resulting absence of CD59 leaves red blood cells unprotected against membrane attack complex assembly, producing chronic complement-mediated intravascular hemolysis.