Ca2+-mediated association of human serum amyloid P component with heparan sulfate and dermatan sulfate.
The serum amyloid P component (SAP) is a precursor glycoprotein of amyloid P component found in all types of amyloid deposits. The binding of human SAP to heparan sulfate and dermatan sulfate was studied using Sepharose-immobilized SAP. The apparent dissociation constants of heparan sulfate and dermatan sulfate for immobilized-SAP were estimated to be approximately 2 X 10(-7) M in the presence of 2 mM CaCl2 at neutral pH and physiological ionic strength. Both the binding affinity of SAP for these glycosaminoglycans and the numbers of binding sites of SAP depended on calcium concentration. Cadmium partially substituted for calcium as an activator of glycosaminoglycan binding to SAP. No binding occurs in the absence of added metal, or in the presence of barium, copper, magnesium, manganese, and strontium. The calcium-dependent binding of [3H]heparan sulfate and [3H]dermatan sulfate to SAP was strongly inhibited by heparan sulfate, heparin, and dermatan sulfate. Chondroitin 6-sulfate was a moderate inhibitor, whereas hyaluronic acid, chondroitin 4-sulfate, and keratan sulfate were not potent inhibitors. The calcium-dependent binding of amyloid P component to heparan sulfate and/or dermatan sulfate may be a cause of the coexistence of the particular glycoprotein and these glycosaminoglycans in amyloid tissues.
D000818:Animals; D002104:Cadmium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002807:Chondroitin / Q000031:analogs & derivatives*; D002850:Chromatography, Gel; D003300:Copper / Q000378:metabolism; D003871:Dermatan Sulfate / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007632:Keratan Sulfate / Q000378:metabolism; D009994:Osmolar Concentration; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology
D002104:Cadmium; D002118:Calcium; D002807:Chondroitin; D003300:Copper; D003871:Dermatan Sulfate; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D007632:Keratan Sulfate; D000683:Serum Amyloid P-Component; D012965:Sodium Chloride