Membrane Attack Complex (MAC)
A multi-protein pore formed by complement proteins C5b through C9 that creates holes in target cell membranes, causing cell death. In myasthenia gravis, MAC formation at the neuromuscular junction worsens muscle weakness. Zilucoplan prevents MAC formation by inhibiting C5.
Technical Context
MAC assembly: C5b binds C6 → C5b6 complex binds C7 → C5b-7 inserts into lipid bilayer → C8 incorporation deepens membrane insertion → C9 polymerisation (up to 18 C9 molecules form a pore ring approximately 10nm internal diameter) → transmembrane pore allowing free passage of ions and water → osmotic lysis of the target cell. In myasthenia gravis, MAC deposits at the neuromuscular junction postsynaptic membrane → destruction of postsynaptic folds (reducing surface area for AChR expression), direct AChR damage, and endplate remodelling. This complement-mediated damage compounds the direct antibody effects (AChR crosslinking and internalisation). Zilucoplan prevents MAC formation by blocking C5 cleavage upstream. Complement regulation: host cells express membrane complement regulatory proteins (CD55/DAF — accelerates C3/C5 convertase decay; CD59/protectin — blocks C9 insertion, preventing MAC completion) that protect them from complement attack. Pathogens lack these regulators, making them susceptible.