Functional properties of membrane cofactor protein of complement

Biochem J. 1989 Dec 1;264(2):581-8. doi: 10.1042/bj2640581.

Abstract

Membrane cofactor protein (MCP or gp45-70) of the complement system is a cofactor for factor I-mediated cleavage of fluid-phase C3b and C3b-like C3, which opens the thioester bond. In the present study the activity of MCP was further characterized. Unexpectedly, in the absence of factor I, MCP stabilized the alternative- and, to a lesser extent, the classical-pathway cell-bound C3 convertases and thereby enhanced C3b deposition. Soluble MCP, if added exogenously, hardly functioned as cofactor for the cleavage of erythrocyte-bound C3b to iC3b; i.e. its activity, compared with the cofactor activity of factor H, was inefficient, since less than 10% of the bound C3b was MCP-sensitive. Further, exogenously added soluble MCP was also a weak cofactor for the cleavage of C3b bound to zymosan. Likewise, factor I, in the presence of cells bearing MCP, cleaved fluid-phase C3b inefficiently. These results imply that MCP has very little extrinsic cofactor activity for factor I. In contrast, exogenously added MCP and factor I mediated efficient cleavage of erythrocyte-bound C3b if the concentration of Nonidet P40 was sufficient to solubilize the cells. Interestingly, soluble MCP and factor I degraded C3b attached to certain solubilized acceptor membrane molecules more readily than others. The cleavage reaction of fluid-phase and cell-bound C3b by soluble MCP and factor I produced iC3b, but no C3c and C3dg. These and prior data indicate that soluble MCP has potent cofactor activity for fluid-phase C3b or C3b bound to solubilized molecules, but acts inefficiently towards C3b on other cells. This functional profile is unique for a C3b/C4b binding protein and, taken together with its wide tissue distribution, suggests an important role for MCP in the regulation of the complement system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD*
  • CD55 Antigens
  • Cell Line
  • Complement C3-C5 Convertases / metabolism
  • Complement Inactivator Proteins / metabolism
  • Complement System Proteins / metabolism*
  • Guinea Pigs
  • Humans
  • Kinetics
  • Membrane Cofactor Protein
  • Membrane Glycoproteins / isolation & purification
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism
  • Molecular Weight

Substances

  • Antigens, CD
  • CD46 protein, human
  • CD55 Antigens
  • Complement Inactivator Proteins
  • Membrane Cofactor Protein
  • Membrane Glycoproteins
  • Membrane Proteins
  • Complement System Proteins
  • Complement C3-C5 Convertases