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

Area of Science:

• Immunology
• Complement System Biology

Background:

• Human leukocytes possess complement regulatory factor I cofactor activity distinct from C3b/C4b receptor (CR1).
• Understanding these regulatory proteins is crucial for comprehending immune response and self-protection mechanisms.

Purpose of the Study:

• To purify and characterize a novel cofactor protein from human leukocyte cell lines.
• To elucidate the structural and functional properties of this newly identified protein.
• To investigate its role in the complement system and its relationship with other regulatory proteins.

Main Methods:

• Purification of the cofactor protein from human leukocyte cell lines.
• Assessment of structural properties including molecular weight (SDS-PAGE), isoelectric point (pI), amino acid composition, and glycosylation.
• Functional assays to determine cofactor activity for Factor I-mediated cleavage of C3b and interaction with complement components (C3b, C4b).

Main Results:

• The purified protein, named membrane cofactor protein (MCP), has a molecular weight of 45,000-70,000 daltons.
• MCP exhibits specific binding to C3b and C4b, possesses an acidic pI (around pH 4), and is rich in proline.
• It acts as a cofactor for Factor I in C3b cleavage, generating iC3b, and shares properties with complement regulatory proteins CR1, H, and C4bp.

Conclusions:

• MCP is a novel membrane-bound cofactor protein with regulatory functions in the complement system.
• Its functional profile is complementary to decay-accelerating factor (DAF), suggesting a synergistic role in inhibiting complement activation on autologous tissues.
• The widespread distribution of DAF and MCP on peripheral blood cells likely contributes to protecting self-tissues from complement-mediated damage.