Interaction of C1s and C4. A binding phenomenon.
Addition of enzymatically active 125-I-labeled C1s (the esterase which is part of the activated complex protein of serum designated as the first component of complement or C1) to purified C4 (the naturally occurring fourth component of human serum complement) results in binding of a portion of the C1s to C4 as indicated by sucrose density gradient ultracentrifugation. Demonstration of binding requires hemolytically active C4, but not enzymatically active C1s. The latter was demonstrated by using DFP inactivated C1s as well as fragments of C1s produced by prior protease treatment of the C1s. While treatment of C1s with proteases (human leukocyte lysosomal enzymes, trypsin or plasmin) resulted in progressive inactivation of the enzymatic activity, the decline in esteratic activity occurred at a much slower rate than the decline in functional activity (inactivation of C4 in free solution). The data lead to the probable conclusion that C1s contains an enzymatic (or esteratic) site in addition to a binding site. The latter might be important for positioning a large molecule, such as C4, in order to effect proteolytic cleavage at the proper bond and hence prepare C4 to participate in the complement sequence.
D002499:Centrifugation, Density Gradient; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002850:Chromatography, Gel; D003172:Complement C1 / Q000378:metabolism* / Q000494:pharmacology; D003181:Complement C4 / Q000378:metabolism*; D003165:Complement System Proteins / Q000378:metabolism*; D004950:Esterases; D005341:Fibrinolysin; D006801:Humans; D006868:Hydrolysis; D007457:Iodine Radioisotopes; D007531:Isoflurophate / Q000494:pharmacology; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases; D011485:Protein Binding; D014357:Trypsin
D003172:Complement C1; D003181:Complement C4; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D007531:Isoflurophate; D003165:Complement System Proteins; D004950:Esterases; D010447:Peptide Hydrolases; D014357:Trypsin; D005341:Fibrinolysin