Regulation of proteolytic activity of complement factor I by pH: C3b/C4b receptor (CR1) and membrane cofactor protein (MCP) have different pH optima for factor I-mediated cleavage of C3b.
C3b/C4b receptor (CR1) and membrane cofactor protein (MCP) are integral membrane glycoproteins with factor I-dependent cofactor activity. They bind to C3b, allowing factor I to cleave C3b at two sites (first and second cleavage), which results in the generation of C3bi, a hemolytically inactive form which is a ligand for complement receptor type three (CR3). C3bi is further degraded by factor I and CR1 (third cleavage) to C3dg (a ligand for complement receptor type two, CR2) and C3c. Using two different substrates, fluid-phase C3b and cell-bound C3b, the cleavage of C3b by MCP and factor I was compared to that by CR1 and factor I under various conditions. The optimal pH for the first and second cleavage of either substrate was 6.0 for MCP and 7.5 for CR1. The third cleavage was mediated only by CR1 and factor I, the optimal pH being 8.0. Low ionic conditions enhanced the C3b binding and cofactor activity of both CR1 and MCP. The efficiency of binding C3b to CR1 or MCP was maximal at pH 6.2. The isoelectric point (pI) of MCP was acidic (approximately 4.0), while that of CR1 was 6.8. Therefore, compared to CR1, MCP possesses distinct functional profiles relative to C3b-binding and factor I-cofactor activity.
Seya
T
T
Department of Immunology, Center for Adult Diseases, Osaka.
Okada
M
M
Nishino
H
H
Atkinson
J P
JP
D015703:Antigens, CD; D003176:Complement C3 / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D017244:Complement Factor I; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007526:Isoelectric Point; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008744:Methylamines / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism; D017463:Receptors, Complement 3b; D012697:Serine Endopeptidases / Q000378:metabolism*
D015703:Antigens, CD; C497857:CD46 protein, human; D003176:Complement C3; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D008744:Methylamines; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D003179:Complement C3b; C027451:methylamine; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; D017244:Complement Factor I