Characteristics of the binding of human C-reactive protein (CRP) to laminin.
Human CRP binds to the basement membrane protein laminin in vitro in a Ca2+-dependent manner via the phosphorylcholine (PC) binding site of C-reactive protein (CRP). The binding was saturable at a molar ratio of 4 (CRP/laminin). The specificity of the binding was shown by inhibition of binding of labeled CRP to laminin by unlabeled CRP, but not by human IgG. Specific binding was optimal in the presence of 5 mM Ca2+, but did not occur in the absence of Ca2+ or in the presence of EDTA. The binding of Ca2+ to CRP causes a conformational change in the molecule, which is required for binding to PC and to laminin. The PC binding site of CRP was implicated in the binding to laminin on the basis of inhibition by both soluble PC and anti-idiotypic mAbs directed to the TEPC-15 PC-binding idiotype found on mouse antibodies to PC. In addition, mouse mAbs specific for the CRP PC binding site displayed decreased reactivity with CRP already bound to laminin. The binding of CRP to laminin provides a possible explanation for selective deposition of CRP at inflamed sites. The CRP-laminin interaction may serve as a means of concentrating CRP at sites of tissue damage so that the CRP might function as a ligand for leukocytes, an event that will result in removal of necrotic tissue and cell debris.
Swanson
S J
SJ
Department of Microbiology, Ohio State University, Columbus 43210.
McPeek
M M
MM
Mortensen
R F
RF
D000911:Antibodies, Monoclonal; D001665:Binding Sites; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D010767:Phosphorylcholine / Q000378:metabolism; D013379:Substrate Specificity
D000911:Antibodies, Monoclonal; D007797:Laminin; D010767:Phosphorylcholine; D002097:C-Reactive Protein; D002118:Calcium