Effect of divalent metal ions and pH upon the binding reactivity of human serum amyloid P component, a C-reactive protein homologue, for zymosan. Preferential reactivity in the presence of copper and acidic pH.
The serum amyloid P component (SAP) has been found to associate in vitro with a variety of polysaccharide and proteinaceous ligands including the yeast cell wall polysaccharide preparation, zymosan, in the presence of calcium at neutral pH. In the present study, we have investigated the role of copper and zinc and other divalent cations and acidic pH on the binding of SAP to zymosan. We report that binding occurs not only in the presence of calcium, but in the presence of copper, zinc, and cadmium as well. No binding occurs in the absence of added metal, or in the presence of barium, cobalt, magnesium, manganese, or nickel. 125I-SAP binding in the presence of metals is inhibited by presaturating the zymosan surface with unlabeled SAP. Whereas calcium-mediated binding decreases by more than 50% as the pH is lowered to 5, copper-mediated binding increases substantially at the more acidic pH values while zinc-mediated binding is essentially unchanged. These data indicate that, in addition to calcium at neutral pH, copper (and zinc) at neutral and particularly acidic pH values mediates SAP binding to polysaccharide ligands. This suggests that SAP may well be considered a copper- as well as a calcium-dependent protein under certain conditions and that this reactivity is favored under those conditions of lowered pH which may result from metabolic processes occurring at local sites of inflammation.
D000682:Amyloid / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent; D003300:Copper / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D046911:Macromolecular Substances; D011485:Protein Binding; D000683:Serum Amyloid P-Component; D015032:Zinc / Q000494:pharmacology; D015054:Zymosan / Q000378:metabolism*
D000682:Amyloid; D002413:Cations, Divalent; D046911:Macromolecular Substances; D000683:Serum Amyloid P-Component; D003300:Copper; D015054:Zymosan; D015032:Zinc; D002118:Calcium