The proteoglycan decorin binds C1q and inhibits the activity of the C1 complex.
Decorin, a small collagen-binding dermatan sulfate proteoglycan, is widely distributed as a component of extracellular matrices. Using a solid phase binding assay, we showed that decorin bound C1q at physiologic pH and ionic strength. The interaction did not require divalent cations and was time and temperature dependent reaching equilibrium in 4 h at 37 degrees C. Binding was specific and saturable with an apparent dissociation constant of 7.6 x 10(-9) M. Decorin was shown to bind pepsin-derived fragments containing the collagenous domain of C1q and collagenase-derived fragments containing the globular domain of C1q. Because these fragments share a short sequence of amino acids, this finding suggests that decorin binds to a region of C1q located near the junction of the two domains. Competition studies using purified preparations of the decorin core protein and the glycosaminoglycan chains showed that only the former inhibited binding of decorin to C1q indicating that the interaction is mediated by the decorin core protein. Decorin was shown to inhibit the hemolytic activity of purified C1 as well as C1 in normal human serum. Approximately 50% inhibition was observed at a decorin concentration of 2 micrograms/ml. Inhibition was not observed if C1 was bound to Ag-complexed antibody. Furthermore, neither the core protein nor the glycosaminoglycan chain of decorin inhibited C1, indicating that the intact proteoglycan is necessary for functional activity.
Krumdieck
R
R
Division of Hematology-Oncology, University of Alabama, Birmingham 35294.
Höök
M
M
Rosenberg
L C
LC
Volanakis
J E
JE
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism*; D015922:Complement C1q / Q000378:metabolism*; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006461:Hemolysis; D006801:Humans; D066298:In Vitro Techniques; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*
D003174:Complement C1 Inactivator Proteins; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D015922:Complement C1q