Biochemical characterization of membrane cofactor protein of the complement system.
Membrane cofactor protein (MCP; formerly termed glycoprotein 45-70 to indicate its Mr) of complement is a widely distributed iC3/C3b binding protein with co-factor activity. On human mononuclear cells and cell lines and platelets, MCP is a doublet. The two forms differ in Mr by approximately 5 k and the upper species is predominant in most individuals. To further characterize these two forms, limited proteolytic digestions were performed. Of the four peptides produced, three have identical Mr indicating that the molecules are similar proteins. Both forms also have acidic isoelectric points and shift to a less acidic isoelectric point after treatment with neuraminidase. Glycosidase digestions indicate that both species contain N- and O-linked oligosaccharides but that the quantity of sialic acid is greater on the larger one. Pulse-chase experiments demonstrate approximately equal quantities of two precursor forms with Mr of 41 and 43 k. These two precursors possess N-linked high-mannose type of oligosaccharides and chase into the mature molecules which have complex sugars. The smaller precursor chases at a slower rate, possibly accounting for the reduced quantity of the smaller form of the mature form of MCP. These experiments indicate that the two forms of MCP are structurally similar and are derived from two distinct precursors. They also suggest that variations in the rate of processing of two intracellular precursors may account for the different quantities of the mature forms of this membrane protein.
D015703:Antigens, CD; D002236:Carbohydrate Conformation; D002460:Cell Line; D003165:Complement System Proteins / Q000032:analysis*; D006026:Glycoside Hydrolases; D006801:Humans; D007525:Isoelectric Focusing; D007963:Leukocytes, Mononuclear / Q000032:analysis / Q000378:metabolism; D016177:Macrophage-1 Antigen; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000302:isolation & purification*; D009439:Neuraminidase; D010449:Peptide Mapping; D011498:Protein Precursors / Q000378:metabolism; D011951:Receptors, Complement / Q000302:isolation & purification
D015703:Antigens, CD; C497857:CD46 protein, human; D016177:Macrophage-1 Antigen; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D011951:Receptors, Complement; D003165:Complement System Proteins; D006026:Glycoside Hydrolases; D009439:Neuraminidase