[Structure and function of a cell-associated complement regulatory protein, membrane cofactor protein (MCP)].

Based on evidence suggesting that human leukocytes have factor I cofactor activity that is distinct from C3b/C4b receptor (CR1), we purified the cofactor protein from several human leukocyte cell-lines, and its structural and functional properties assessed. This protein migrates Mr 45,000-70,000 dalton region with a broad singlet or doublet on SDS-PAGE, specifically binds to C3b and C4b, has an acidic pI around pH 4, is rich in proline in amino acid analysis, possesses both N-linked and O-linked oligosaccharides, generates iC3b by acting as a cofactor for I-mediated C3b cleavage, and does not disassemble the C3 convertases. This protein therefore shares some common properties characteristic to complement regulatory proteins, CR1, H, and C4b-binding protein (C4bp). In addition, the functional profile of this protein is complementary to that of decay-accelerating factor (DAF) that has been known to be a protective protein for complement-mediated cell damage. We named this protein membrane cofactor protein (MCP), and suspect that the reason DAF and MCP are widely distributed on human peripheral blood cells relates to their synergistic activity profile such that complement activation on autologous tissue is inhibited.